Fact-checked by Grok 2 weeks ago

Dendritic cell

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) of the mammalian immune system, derived from hematopoietic stem cells (HSCs) in the bone marrow, that serve as a critical bridge between innate and adaptive immunity by capturing pathogens or antigens in peripheral tissues, processing them, and presenting peptide fragments via major histocompatibility complex (MHC) molecules to naïve T lymphocytes, thereby initiating antigen-specific immune responses or enforcing tolerance to self-antigens and harmless environmental components.^[1]^[2] DCs were first identified in 1973 by Ralph Steinman and Zanvil Cohn through morphological studies of mouse spleen cells using phase-contrast microscopy, revealing their distinctive dendritic projections, though earlier observations of similar cells in human epidermis date back to 1868 by Paul Langerhans.^[1]^[2] These cells form a distributed network across lymphoid organs (such as lymph nodes and spleen) and non-lymphoid tissues (including skin, lungs, and gut), where they constantly survey for danger signals like microbial patterns or tissue damage.^[1] Upon activation by pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), DCs undergo maturation, upregulating co-stimulatory molecules (e.g., CD80, CD86) and chemokine receptors (e.g., CCR7) to migrate to draining lymph nodes via lymphatic vessels, guided by chemokines such as CCL19 and CCL21.^[1]^[3] DCs comprise distinct subsets with specialized functions, broadly categorized into conventional or classical DCs (cDCs), plasmacytoid DCs (pDCs), and monocyte-derived DCs (moDCs).^[1]^[2] cDCs, including cross-presenting CD8α⁺ or CD103⁺ subsets and CD11b⁺ subsets, excel at priming CD8⁺ and CD4⁺ T cells for cytotoxic or helper responses, respectively, and are essential for directing T cell differentiation toward specific effector types like Th1, Th2, Th17, or regulatory T cells (Tregs).^[1] pDCs specialize in rapid type I interferon production upon viral recognition via Toll-like receptors (TLRs), bolstering antiviral defenses and activating innate lymphocytes such as natural killer (NK) cells.^[1]^[2] In contrast, moDCs emerge from monocytes during inflammation or infection, contributing to adaptive responses in non-steady-state conditions, while Langerhans cells represent a tissue-resident subset in the epidermis focused on skin immunity.^[2] Beyond antigen presentation, DCs orchestrate broader immune regulation by secreting cytokines (e.g., IL-12 for Th1 polarization, IL-23 for Th17) and integrating signals from the microenvironment to balance immunity against pathogens, tumors, or allergens with tolerance to prevent autoimmunity.^[1]^[3] Their migration dynamics, influenced by metabolic reprogramming, cytoskeletal remodeling, and epigenetic changes, are pivotal in inflammation, where dysregulated DC function contributes to diseases like autoimmunity, chronic infections, and cancer.^[3] As master regulators, DCs are targeted in immunotherapies, including cancer vaccines and tolerance induction for transplantation, underscoring their therapeutic potential.^[2]

Overview

Definition and characteristics

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that serve as immunological sentinels, bridging innate and adaptive immunity by capturing, processing, and presenting antigens to initiate immune responses.^[4] They are uniquely equipped to activate naive T cells, a capability that distinguishes them from other immune cells and enables the priming of adaptive immunity against pathogens while maintaining tolerance to self-antigens.^[5] Unlike macrophages, which primarily focus on phagocytosis and microbial killing, or B cells, which mainly stimulate memory T cells and produce antibodies, DCs excel in efficient antigen uptake, processing, and migration to lymphoid organs for T cell activation.^[4] Morphologically, DCs exhibit a characteristic stellate shape with multiple dendritic projections that extend from the cell body, facilitating extensive surface area for antigen sampling in tissues.^[6] In their immature state, they display high endocytic activity through mechanisms such as macropinocytosis and receptor-mediated endocytosis, allowing them to internalize large volumes of extracellular material—approximately 2–3 times their own volume per hour.^[7] Upon maturation, these cells upregulate major histocompatibility complex (MHC) class II molecules and costimulatory proteins like CD80 and CD86, which are essential for delivering activation signals to T cells.^[6] DCs are widely distributed throughout the body, residing in peripheral tissues such as the skin—where they are known as Langerhans cells—the mucosal surfaces of the lungs and intestines, as well as in blood, lymph nodes, and other lymphoid organs like the spleen and thymus.^[5] This strategic positioning allows them to act as frontline sensors, continuously surveying the environment for potential threats before migrating to secondary lymphoid tissues to orchestrate T cell responses.^[4]

Discovery and historical context

Dendritic cells were first identified in 1973 by Ralph M. Steinman and Zanvil A. Cohn during their studies of mouse spleen cell suspensions at The Rockefeller University. Using phase-contrast microscopy, they observed a rare population of cells (comprising about 1% of splenocytes) characterized by prominent, dynamic dendrite-like processes that extended and retracted, distinguishing them from typical macrophages and other leukocytes. Electron microscopy further revealed their lack of phagocytic vacuoles and unique intracellular structures, leading the researchers to initially speculate they might represent a novel type of fixed connective tissue cell or a specialized macrophage variant.^[8] The cells were named "dendritic cells" by Steinman and Cohn, derived from the Greek word dendron meaning tree, to reflect their branching morphology. Throughout the 1970s and 1980s, subsequent research in Steinman's laboratory focused on their functional properties, particularly their exceptional capacity for antigen presentation. Dendritic cells were shown to stimulate T-cell proliferation in mixed leukocyte reactions at concentrations 100 times lower than those required for other splenocytes, and they effectively presented haptens to prime T helper cells for antibody responses. These findings established dendritic cells as key initiators of adaptive immunity, shifting the paradigm from macrophages as primary antigen presenters.^[8]^[9]^[10] In the 1990s, dendritic cells were identified in humans, beginning with their isolation from peripheral blood as large, lineage-negative cells expressing high levels of MHC class II molecules. Early work by Wesley C. van Voorhis and colleagues in the early 1980s had hinted at their presence in human blood, but refined techniques in the 1990s, including density gradient separation and culture in monocyte-conditioned medium, confirmed their maturation into potent immunostimulatory cells distinct from monocytes. By the 2000s, advancements in flow cytometry and genetic markers enabled precise subset classification; for instance, blood dendritic cell antigen (BDCA) markers such as BDCA-1 (CD1c), BDCA-2, and BDCA-3 were identified to delineate myeloid and plasmacytoid subsets, facilitating comparative studies with mouse models.^[8]^[11] Steinman's groundbreaking contributions culminated in the 2011 Nobel Prize in Physiology or Medicine, awarded for the discovery of dendritic cells and their role in adaptive immunity, despite his recent passing. This recognition underscored the cells' foundational importance in immunology, building on decades of meticulous observational and functional studies.^[12]

Classification

Conventional dendritic cells

Conventional dendritic cells (cDCs) represent the primary antigen-presenting cell population within the dendritic cell family, distinguished by their ability to prime naïve T cells in lymphoid tissues after capturing antigens in peripheral sites.^[13] They originate from bone marrow hematopoietic stem cells through a series of progenitors, including common dendritic cell progenitors (CDPs) and pre-DCs, which circulate and seed peripheral tissues where they differentiate into mature subsets.^[14] In both humans and mice, cDCs are broadly classified into three main subsets—cDC1, cDC2, and cDC3—based on distinct transcriptional programs, surface markers, and functional roles, with cDC1 specializing in cross-presentation to CD8+ T cells and cDC2 focusing on CD4+ T cell activation.^[15]^[16] The cDC1 subset is characterized in humans by expression of CD141 (also known as BDCA-3), XCR1, CLEC9A, and CADM1, while in mice, it is identified by CD8α (in spleen and lymph nodes), CD103 (in non-lymphoid tissues), XCR1, and DEC-205.^[13] These cells are found in lymphoid organs such as the T cell zones of lymph nodes and spleen, as well as in barrier tissues including skin, lung, intestine, and liver, where tissue-specific variants like CD103+ cDC1s predominate in mucosa and dermis.^[14] Functionally, cDC1s excel at MHC class I cross-presentation of exogenous antigens to CD8+ T cells, promoting cytotoxic responses and Th1 differentiation, a specialization driven by transcription factors like IRF8 and Batf3.^[15] In contrast, the cDC2 subset expresses CD1c and SIRPα (CD172a) in humans, alongside CD11b and CD11c, whereas in mice, it is marked by CD11b, CD172a, and variable CD103 or CCR2 depending on the tissue.^[13] cDC2s reside in similar locations to cDC1s but often enrich at T-B cell borders in lymphoid organs and in the dermis or lamina propria of skin and mucosa, with migratory forms reaching draining lymph nodes via CCR7.^[14] Their primary role involves MHC class II presentation of antigens to CD4+ T cells, driving Th2, Th17, or Tfh responses, and they can also contribute to cross-presentation under certain activating conditions, influenced by local cytokines like GM-CSF for survival.^[15] The cDC3 (DC3) subset, increasingly recognized as a distinct conventional DC population as of 2025, originates from monocyte-dendritic cell progenitors (MDPs) in the bone marrow and is prominent in inflammatory contexts. In humans, cDC3s are identified by markers such as CD14, CD163, HLA-DR, and CD11c, while in mice, they express CD11b^hi and CD64^+. Functionally, cDC3s contribute to antigen presentation to both CD4^+ and CD8^+ T cells, particularly in infections, chronic inflammation, and cancer, where they can promote Th1/Th17 responses or antitumor immunity depending on the microenvironment.^[16] Tissue microenvironments further tailor cDC functions, such as cDC2s in the skin inducing Th2 immunity against allergens or cDC1s in the lung sampling epithelial antigens for CD8+ T cell priming, ensuring adaptive responses match the site of infection or challenge.^[14]

Plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDCs) represent a specialized subset of dendritic cells distinguished by their plasma cell-like morphology, featuring abundant rough endoplasmic reticulum and a prominent Golgi apparatus in their immature state, which transforms into a dendritic-like form upon activation.^[17] They are characterized by high expression of Toll-like receptors 7 and 9 (TLR7 and TLR9), enabling rapid sensing of viral single-stranded RNA and bacterial CpG DNA, respectively.^[18] Upon pathogen recognition, pDCs produce vast quantities of type I interferons, including IFN-α and IFN-β, within 1–3 hours, far exceeding the capacity of other immune cells.^[18] pDCs are identified by specific surface markers, such as BDCA-2 (CD303), CD123 (the α chain of the IL-3 receptor), CD4, CD45RA, and BDCA-4 (CD304), which distinguish them from other leukocyte populations.^[17] In humans, these markers are commonly used for isolation and flow cytometric identification, while in mice, equivalents include B220, Siglec-H, and Ly49Q.^[19] Unlike conventional dendritic cells, pDCs exhibit limited phagocytic activity and endocytosis, reflecting their specialization in cytokine secretion over antigen uptake.^[19] Regarding origin, pDCs develop in the bone marrow from hematopoietic stem cells through both myeloid and lymphoid pathways, originating from common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs) via Flt3-positive common dendritic cell progenitors (CDPs).^[19] This dual ontogeny is regulated by the cytokine Flt3 ligand (Flt3L) and transcription factors such as E2-2 (encoded by TCF4), which is essential for pDC commitment and IRF7 expression to drive IFN production.^[18] Seminal studies have established that E2-2 deficiency leads to profound pDC depletion, underscoring its pivotal role. pDCs are primarily located in the blood, where they constitute 0.1–0.5% of peripheral blood mononuclear cells (PBMCs), as well as in the bone marrow and secondary lymphoid tissues like lymph nodes and spleen.^[17] They recirculate through the periphery via high endothelial venules and chemokine receptors such as CCR9 and CXCR4, with minor populations residing in non-lymphoid tissues like skin and mucosa under steady-state conditions.^[19] Functionally, pDCs serve as key sentinels in innate antiviral defense by secreting type I IFNs, which inhibit viral replication, activate natural killer cells, and promote an antiviral state in surrounding cells.^[18] This IFN production bridges innate and adaptive immunity by enhancing T-cell priming and B-cell responses, although pDCs exhibit weaker antigen presentation capabilities compared to conventional dendritic cells, with a preference for MHC class II-restricted CD4+ T-cell activation over cross-presentation to CD8+ T cells.^[17] Their rapid IFN response positions pDCs as an early alert system for viral infections, as demonstrated in foundational work identifying them as the primary IFN-α-producing cells in response to herpes simplex virus.^[20]

Derived and other subsets

Monocyte-derived dendritic cells (moDCs) are generated from circulating monocytes in response to inflammatory signals, particularly during infections or tissue damage, where granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) drive their differentiation in vivo.^[21] These cells closely mimic the phenotype and function of immature dendritic cells, expressing markers such as CD1c and MHC class II, and they rapidly acquire antigen-presenting capabilities upon recruitment to inflamed sites.^[22] In vitro, moDCs are commonly produced by culturing isolated CD14+ monocytes with GM-CSF and IL-4 for 5–7 days, resulting in cells that exhibit high endocytic activity and the ability to stimulate T cell responses, making them a key model for studying DC biology. In vitro-generated dendritic cell subsets are produced in laboratories using specific cytokine combinations to expand or differentiate precursors, often for research into immune activation and vaccine development. For instance, Flt3 ligand (Flt3L) is used to culture bone marrow-derived pre-dendritic cells (pre-DCs), yielding populations enriched in cross-presenting cells that enhance antitumor immunity in preclinical vaccine studies.^[23] These lab-generated DCs, which can include moDC-like or conventional DC mimics, allow controlled manipulation of antigen loading and maturation, facilitating experiments on T cell priming without reliance on in vivo variability.^[24] Other variants include Langerhans cells, which are skin-specific dendritic cells residing in the epidermis and characterized by high expression of CD1a and langerin (CD207), enabling them to capture antigens in the stratified squamous environment.^[25] In the tumor microenvironment, inflammatory dendritic cells emerge as a distinct subset, often derived from monocytes under chronic inflammation, and they express markers like CD1c while promoting both pro- and anti-tumor responses through cytokine secretion.^[21]^[26] These derived subsets differ from steady-state dendritic cells in their context-dependent generation, arising primarily during inflammation rather than constitutive hematopoiesis, and they typically exhibit a shorter lifespan, often surviving only days to weeks before apoptosis, which limits their persistence compared to tissue-resident populations.00299-3)30213-2) Originating from monocyte progenitors in the bone marrow, their rapid turnover supports acute immune responses but requires ongoing recruitment for sustained activity.^[21]

Development and lifecycle

Ontogeny and progenitors

Dendritic cells (DCs) originate from hematopoietic stem cells in the bone marrow, deriving primarily from common myeloid progenitors (CMPs) and, to a lesser extent, common lymphoid progenitors (CLPs), with CMPs showing greater efficiency in generating splenic and lymph node conventional DCs (cDCs).^[27] These progenitors commit to the DC lineage through sequential intermediates, including the macrophage-DC progenitor (MDP) and the common DC progenitor (CDP), identified in mice as Lin⁻ c-Kitᵐᵒᵈ Flt3⁺ M-CSFR⁺ cells that lack macrophage potential but give rise to both cDCs and plasmacytoid DCs (pDCs).^[27] In humans, a analogous pathway exists, with CD34⁺ hematopoietic stem and progenitor cells (HSPCs) from the bone marrow differentiating into monocyte-DC progenitors or CDPs that produce pDCs and pre-cDCs.^[28] Human multipotent lymphoid progenitors (MLPs, Lin⁻ CD34⁺ CD38⁻ CD45RA⁺ CD10⁺) are particularly efficient at generating cDC1s (CD141⁺ DNGR-1⁺), outperforming CMPs, which favor cDC2s and monocytes.^[29] Lineage commitment to DCs is tightly regulated by transcription factors, with PU.1 (encoded by Sfpi1) playing a foundational role in early hematopoietic differentiation by controlling Flt3 and cytokine receptor expression in a dose-dependent manner; its deficiency abolishes all DC subsets.^[30] IRF8 is essential for pDC and cDC1 development, extinguishing alternative neutrophil fates and promoting DC-specific gene expression, while its absence leads to severe reductions in these subsets.^[31] Batf3 further specifies cDC1s by maintaining IRF8 levels and inducing markers like CD103 and Langerin, with Batf3⁻/⁻ mice lacking CD8α⁺ and CD103⁺ cDCs.^[31] In humans, IRF8 mutations similarly impair CD141⁺ cDC development, underscoring conserved mechanisms across species.^[28] Differentiation from CDPs proceeds in an Flt3 ligand (Flt3L)-dependent manner for pDCs and cDCs, as Flt3L signaling through the Flt3 receptor drives proliferation and survival of these progenitors, with Flt3L deficiency markedly reducing DC numbers in both mice and humans.^[27] In contrast, monocyte-derived DCs (moDCs) arise via an M-CSF (CSF-1)-dependent pathway from monocyte-DC progenitors, independent of Flt3L but responsive to GM-CSF in inflammatory contexts.^[27] While the core ontogeny is similar between mice and humans—featuring Flt3L-driven CDP expansion and shared transcription factor requirements—human DCs lack CD8 expression and exhibit subset-specific differences, such as CD1c⁺ DCs deriving from both lymphoid and myeloid lineages with potential for Langerhans cell formation.^[28]

Maturation and migration

Dendritic cells (DCs) in their immature state reside in peripheral tissues and exhibit high phagocytic and endocytic activity, enabling efficient antigen capture, while expressing low levels of costimulatory molecules such as CD80 and CD86.^[3] This state positions immature DCs as sentinels for environmental surveillance, with limited capacity to activate T cells due to subdued MHC class II and accessory molecule expression.^[32] Maturation of DCs is primarily triggered by pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS), recognized through Toll-like receptors (TLRs) on the cell surface.^[33] This recognition initiates intracellular signaling cascades that drive phenotypic changes, including the upregulation of MHC class II molecules for enhanced antigen presentation and CD40 for improved interactions with T cells.^[3] Additionally, maturation involves a coordinated downregulation of receptors for inflammatory chemokines, shifting the DCs' responsiveness to guide their relocation.^[34] Upon maturation, DCs undergo a programmed migration to draining lymph nodes, mediated by the upregulation of the chemokine receptor CCR7, which responds to ligands CCL19 and CCL21 produced in lymphoid tissues.^[35] This chemotaxis facilitates directional movement through afferent lymphatics, supported by alterations in integrin expression, such as increased LFA-1 (αLβ2) affinity and reduced binding of tissue-retention integrins like VLA-4 (α4β1), promoting egress from peripheral sites.^[32] These changes ensure that antigen-loaded DCs efficiently traffic to sites of T cell priming. DC maturation progresses through distinct stages: an early phagocytic phase where antigen uptake predominates, a late antigen-processing phase involving intracellular trafficking and peptide loading onto MHC molecules, and a fully mature stage optimized for T cell activation through high surface expression of stimulatory ligands.^[3] This stepwise transformation, often initiated in tissues derived from committed progenitors, enhances the adaptive immune response by linking peripheral antigen detection to central lymphoid activation.^[34]

Lifespan and turnover

Dendritic cells (DCs) exhibit short lifespans at steady state, with conventional DCs (cDCs) in peripheral tissues typically surviving 3-7 days before undergoing apoptosis and turnover, while plasmacytoid DCs (pDCs) circulate in the blood for approximately 2-3 days.^[36]^[37]^[38] This rapid replacement ensures continuous surveillance, as DC populations are replenished from bone marrow-derived progenitors entering the circulation.^[36] In lymphoid organs, pDCs show similarly brief residence times, with near-complete replacement within 3 days via blood-borne influx.^[37] Recent kinetic studies using in vivo deuterium-glucose labeling have refined estimates of human DC turnover, revealing subset-specific half-lives in circulation: activated/semi-mature DCs (ASDCs) at ~2.16 days, cDC1 at ~1.32 days, and cDC2 at ~2.20 days upon release from the bone marrow.^[39] These findings, modeled via Bayesian approaches, highlight the ephemeral nature of circulating DCs, with low proliferation rates (e.g., 0.49-1.03 day⁻¹ across subsets) underscoring reliance on steady influx rather than local expansion.^[39] During inflammation, such as cutaneous responses, DC recruitment to sites prolongs their functional presence by altering migration and phenotype, effectively extending overall population dynamics beyond steady-state kinetics.^[39] DC longevity is tightly regulated by apoptosis pathways involving the BCL-2 family, where prosurvival members like BCL-2 confer distinct identities: pDCs heavily depend on BCL-2 for mitochondrial integrity and survival, whereas cDCs express varied antiapoptotic profiles (e.g., higher MCL-1).^[40] Homeostatic proliferation is driven by Flt3 ligand (Flt3L), which promotes DC precursor expansion and maintenance without inducing excessive apoptosis, ensuring balanced turnover.^[36] Turnover exhibits significant heterogeneity across DC subsets and organs; for instance, gut or airway cDCs may persist 7-13 days due to local environmental cues, contrasting shorter splenic residence, while pDC kinetics vary by activation state and tissue migration delays.^[37]^[36] This variability complicates precise modeling but emphasizes adaptive population control tailored to immune needs.^[39]

Functions

Antigen presentation mechanisms

Dendritic cells (DCs) serve as key antigen-presenting cells, processing exogenous antigens through distinct pathways to load peptides onto major histocompatibility complex (MHC) class II molecules for presentation to CD4+ T cells. Exogenous antigens, internalized via endocytosis or phagocytosis, are directed to endosomal compartments where they undergo proteolytic degradation by acid hydrolases such as cathepsins.^[41] The resulting peptides are then loaded onto MHC class II molecules within these MHC class II compartments (MIICs), facilitated by the removal of the invariant chain (Ii), which acts as a chaperone to prevent premature peptide binding and directs MHC II trafficking from the endoplasmic reticulum (ER) to endosomes.81458-0) Ii degradation is sequentially mediated by proteases like cathepsin S, enabling stable peptide-MHC II complex formation for surface expression.^[42] In parallel, DCs employ cross-presentation to display exogenous antigens on MHC class I molecules, priming CD8+ T cells against extracellular threats. This process routes internalized antigens into TAP-independent pathways, such as the vacuolar route, where endosomal proteases generate peptides directly within phagosomes or lysosomes without cytosolic export, bypassing the need for transporter associated with antigen processing (TAP).^[43] These peptides bind recycling or newly synthesized MHC class I molecules in endocytic compartments, often under neutral pH conditions to preserve peptide integrity.^[44] Effective T cell activation requires costimulatory signals beyond antigen-MHC-TCR engagement. DCs express B7 molecules (CD80 and CD86), which ligate CD28 on T cells to deliver signal 2, promoting IL-2 production and proliferation; this interaction is indispensable for full activation of naive T cells.^[45] Additionally, intercellular adhesion molecule-1 (ICAM-1) on DCs binds LFA-1 (CD11a/CD18) on T cells, stabilizing the immunological synapse and enhancing sustained signaling.^[46] DCs exhibit high efficiency in antigen processing due to specialized machinery. For MHC class I presentation, elevated proteasome activity rapidly degrades antigens into peptides suitable for loading, particularly in subsets like conventional DC1 (cDC1).^[47] The invariant chain ensures efficient MHC II trafficking and peptide selection, with its regulated proteolysis controlling the balance between antigen presentation and tolerance in immature DCs.81458-0) Among DC subsets, cDC1 are particularly adept at cross-presentation through proteasomal degradation, exporting exogenous antigens to the cytosol for processing by the immunoproteasome and subsequent TAP-dependent transport into the ER for MHC class I loading.^[48] This mechanism underscores cDC1's role in initiating cytotoxic responses.

Cytokine and chemokine production

Dendritic cells (DCs) secrete a variety of cytokines and chemokines that modulate the immune environment, influencing T cell differentiation, recruitment, and overall response polarity. These soluble factors are produced in response to pathogen recognition and environmental cues, enabling DCs to bridge innate and adaptive immunity. Production is tightly regulated and varies by DC subset, with conventional DCs (cDCs) favoring pro-inflammatory profiles and plasmacytoid DCs (pDCs) specializing in antiviral responses.^[49] Conventional DCs, particularly the cDC1 subset (CD8α⁺ or CD103⁺), are major producers of interleukin-12 (IL-12), a key cytokine that promotes Th1 differentiation and interferon-γ (IFN-γ) production by T cells. IL-12 secretion is triggered by Toll-like receptor (TLR) signaling through pathways involving MyD88 and c-Rel transcription factors, often in synergy with antigen presentation to enhance cytotoxic responses. In contrast, the cDC2 subset (CD11b⁺) predominantly secretes IL-23 and IL-6, driving Th17 cell development and inflammatory responses, while also producing chemokines such as CCL3, CCL4, and CCL5 to attract innate immune cells. Monocyte-derived DCs (moDCs) exhibit versatile cytokine profiles, including tumor necrosis factor-α (TNF-α), adaptable to inflammatory contexts.^[49]^[50]^[51] Plasmacytoid DCs rapidly produce high levels of type I interferons, including IFN-α and IFN-β, upon viral recognition via TLR7 and TLR9, mediated by constitutive expression of IRF7. This antiviral cytokine burst helps establish an early immune barrier and activates neighboring cells. For tolerance induction, certain DC subsets, such as intestinal CD103⁺ cDCs, produce or activate transforming growth factor-β (TGF-β) through integrin αvβ8, promoting regulatory T cell (Treg) differentiation and maintaining mucosal homeostasis.^[49]^[50]00907-3/fulltext) Regarding chemokines, mature DCs secrete CCL19 to facilitate T cell recruitment and clustering in lymphoid tissues, complementing their role in antigen presentation. Additionally, DCs produce CXCL10, which attracts CXCR3-expressing effector T cells and NK cells to sites of inflammation, enhancing localized immune surveillance. These chemokine outputs are upregulated by TLR ligands, ensuring coordinated migration and amplification of adaptive responses.^[52]^[53]^[54]

Regulation of immune responses

Dendritic cells (DCs) play a pivotal role in regulating immune responses by balancing activation and suppression, thereby preventing excessive inflammation while mounting effective defenses against pathogens. In steady-state conditions, immature or semi-mature DCs adopt a tolerogenic phenotype that promotes peripheral tolerance and inhibits autoimmunity. These tolerogenic DCs express molecules such as programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO), which interact with T cells to induce regulatory T cells (Tregs) and dampen pro-inflammatory responses.^[55]^[56] The transition between immunogenic and tolerogenic DC states is tightly controlled by environmental signals and molecular interactions. For instance, engagement of CTLA-4 on T cells with CD80/CD86 on DCs delivers inhibitory signals that favor tolerogenesis, suppressing DC maturation and cytokine production. Similarly, environmental cues like vitamin D3 can reprogram DCs toward a tolerogenic profile by upregulating IDO and IL-10, enhancing their ability to induce Tregs.^[57]^[58] This switch ensures that DCs respond appropriately to context, such as distinguishing harmless self-antigens from threats. In peripheral tolerance, DCs contribute to the maintenance of self-tolerance by promoting anergy or deletion of self-reactive T cells that escape central tolerance mechanisms. Immature DCs presenting self-antigens in the absence of costimulatory signals induce T cell anergy, rendering autoreactive clones functionally unresponsive. Additionally, DCs can facilitate the deletion of activated self-reactive T cells through Fas-FasL interactions or by creating a pro-apoptotic microenvironment.^[59]^[60]^[61] Feedback loops involving DC-T cell interactions further refine immune regulation, exemplified by DC licensing. CD4+ T cells provide help to DCs via CD40L-CD40 engagement, which licenses DCs for enhanced antigen presentation and cytokine secretion, such as IL-12, to promote adaptive responses while preventing tolerance breakdown. This bidirectional signaling ensures coordinated immune activation without unchecked escalation.^[62]^[63]

Role in diseases

Involvement in cancer

Dendritic cells (DCs) play a critical role in anti-tumor immunity, but the tumor microenvironment (TME) often impairs their function, leading to immunosuppression. Tumor-derived factors promote the recruitment of regulatory T cells (Tregs) by subverting DCs, which lose their stimulatory capacity for effector T cells and instead foster Treg expansion and activation. This Treg-DC crosstalk in the TME enhances immune tolerance, limiting cytotoxic responses against cancer cells. Additionally, DCs in tumors upregulate PD-L1 expression, often induced by TGF-β, which attenuates T cell activation and induces T cell anergy, further dampening anti-tumor immunity. Impaired DC maturation is another hallmark, as the TME induces tolerogenic DCs that express immunosuppressive molecules like PD-L1 and produce anti-inflammatory factors, hindering effective antigen presentation. DC subsets exhibit distinct roles in cancer. Conventional type 1 DCs (cDC1s) are essential for priming anti-tumor CD8+ T cell responses, as they cross-present tumor antigens via MHC class I and produce chemokines like CXCL9 and CXCL10 to recruit and expand cytotoxic T cells within the tumor. In contrast, plasmacytoid DCs (pDCs) display dual functionality: they can promote anti-tumor immunity through type I interferon production that enhances NK cell and T cell activity, but in many tumors, pDCs adopt pro-tumoral roles by inducing Treg differentiation and suppressing effector responses via IDO expression. DC-based immunotherapies aim to harness these cells to overcome TME suppression. Sipuleucel-T, an autologous DC vaccine loaded with prostatic acid phosphatase (PAP) fused to GM-CSF, was the first FDA-approved DC therapy for metastatic castration-resistant prostate cancer, demonstrating a 22% reduction in mortality risk in phase III trials. Recent advances as of 2025 include ex vivo loading of DCs with mRNA encoding neoantigens, which has shown promise in solid tumors like melanoma and glioblastoma by eliciting robust, personalized CD8+ T cell responses and improving progression-free survival in early-phase trials.^[64]^[65] Despite these strategies, challenges persist due to tumor-derived factors that inhibit DC function. Indoleamine 2,3-dioxygenase (IDO), upregulated in the TME by tumor cells and DCs, catabolizes tryptophan to generate immunosuppressive kynurenine, which promotes Treg induction and DC tolerance, thereby evading anti-tumor immunity. Targeting IDO has emerged as a complementary approach to enhance DC vaccines, though clinical translation remains limited by compensatory immunosuppressive pathways in the TME.

Autoimmunity and tolerance

Dendritic cells (DCs) are pivotal in establishing and maintaining peripheral tolerance to self-antigens, primarily through tolerogenic subsets that induce regulatory T cells (Tregs) and anergy in autoreactive T cells. However, dysregulation of DC function, such as impaired tolerogenic programming or excessive maturation, can lead to failed tolerance and autoimmunity by promoting effector T cell responses against self-antigens. In autoimmune diseases, conventional DC type 2 (cDC2) subsets, which are specialized in CD4+ T cell priming, become overactive and present self-antigens in an inflammatory context, driving differentiation of T helper 17 (Th17) cells that exacerbate tissue damage through IL-17-mediated inflammation.^[66]^[67] Defects in tolerogenic DCs (tolDCs) are particularly evident in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), where reduced numbers or dysfunctional tolDCs fail to suppress autoreactive responses. In SLE, plasmacytoid DCs (pDCs) and conventional DCs exhibit heightened activation, leading to excessive type I interferon production and impaired induction of Tregs, thereby perpetuating autoantibody production and immune complex deposition. Similarly, in RA, synovial tolDCs show altered maturation and reduced expression of suppressive molecules like PD-L1, contributing to chronic joint inflammation by sustaining Th1 and Th17 responses. Recent 2024 studies highlight dysregulated DC subsets in SLE, with mature DCs overexpressing chemokines like CCL2, which disrupts immune homeostasis and promotes neuroinflammation in neuropsychiatric manifestations.^[68]^[67] As of 2025, phase I/II trials of tolerogenic DC infusions in SLE patients show preliminary efficacy in reducing disease activity scores without systemic immunosuppression.^[69] In type 1 diabetes (T1D), islet-resident DCs, particularly CD11b+ and CD103+ subsets, constitutively present β-cell-derived self-antigens such as insulin peptides to autoreactive CD4+ and CD8+ T cells in pancreatic lymph nodes, initiating insulitis and β-cell destruction. Likewise, in multiple sclerosis (MS), DCs within central nervous system lesions uptake myelin components and present them to myelin-specific T cells, promoting Th17-mediated demyelination and chronic inflammation. These examples underscore how DC-mediated self-antigen presentation shifts from tolerance to pathogenicity in specific autoimmune contexts.^[70]^[71] Therapeutic strategies targeting DCs aim to restore tolerance by modulating their function, with rapamycin emerging as a key agent that conditions DCs toward a tolerogenic phenotype. Rapamycin inhibits mTOR signaling in DCs, preventing upregulation of costimulatory molecules like CD40 while preserving PD-L1 expression, thereby enhancing Treg induction and reducing allostimulatory capacity in models of autoimmunity. Clinical trials have demonstrated safety and preliminary efficacy of rapamycin-treated tolDCs in RA, with intra-articular administration suppressing joint inflammation without broad immunosuppression. Genetic factors, such as mutations in the transcription factor IRF8, further link DC dysfunction to immune dysregulation; biallelic IRF8 variants cause profound DC and monocyte deficiency, leading to severe immunodeficiency with impaired antigen presentation; certain IRF8 polymorphisms are associated with autoimmune diseases like SLE through altered type I IFN production.^[72]^[67]^[73]^[74]

Infections and neoplasms

Dendritic cells (DCs) play a pivotal role in orchestrating immune responses to viral infections, with plasmacytoid DCs (pDCs) serving as primary producers of type I interferons (IFN-I) upon recognition of viral pathogens. In human immunodeficiency virus (HIV) infection, pDCs rapidly secrete high levels of IFN-α in response to viral exposure, bridging innate and adaptive immunity by activating natural killer cells and T lymphocytes, though chronic HIV leads to pDC depletion and functional impairment. Similarly, during influenza A virus infection, pDCs mount a robust antiviral program characterized by IFN-α production and upregulation of genes involved in antigen presentation and T cell costimulation, enhancing early viral containment. Conventional DCs (cDCs), particularly the CD103+ subset, facilitate cross-presentation of viral antigens from infected cells onto MHC class I molecules, priming cytotoxic T lymphocytes (CTLs) essential for clearing HIV- and influenza-infected cells. This process is critical for generating virus-specific CD8+ T cell responses, as demonstrated in models of influenza where cDC-mediated cross-priming protects against lethal challenge. In chronic viral infections such as hepatitis C virus (HCV), DCs undergo exhaustion, marked by reduced IL-12 production and impaired T cell stimulatory capacity, which correlates with CD8+ T cell dysfunction and viral persistence. HCV core protein inhibits pDC function through monocyte-mediated mechanisms, leading to diminished IFN-α output and accelerated pDC loss, thereby sustaining chronicity. This exhaustion is linked to altered DC maturation and antigen presentation, contributing to ineffective CTL responses observed in up to 70% of infected individuals progressing to chronic disease. DCs also respond to bacterial and fungal pathogens through Toll-like receptor (TLR) signaling, which triggers maturation and directs T helper cell differentiation. TLR2 and TLR4 activation by bacterial components promotes DC secretion of IL-12 and IL-23, favoring Th1 and Th17 responses that enhance macrophage activation and neutrophil recruitment against extracellular bacteria. In fungal infections like candidiasis, Dectin-1 and TLR4 synergy on DCs drives Th17 polarization, enabling protective antifungal immunity while preventing pathogenic inflammation; deficiencies in this pathway exacerbate disseminated disease. Monocyte-derived DCs (moDCs) emerge prominently in sepsis, where accelerated differentiation from circulating monocytes occurs, but results in dysregulated function including reduced IL-12 and increased IL-10 production. In septic patients, moDCs preferentially induce T cell anergy or regulatory T cell expansion, exacerbating immunosuppression and linking to higher mortality rates through impaired antigen presentation. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) represents a rare, aggressive leukemia originating from immature pDC precursors, typically expressing CD4, CD56, and CD123 on blastic cells infiltrating skin, bone marrow, and lymph nodes. Affecting approximately 0.5-1 per million individuals annually, BPDCN presents with cutaneous lesions in nearly 90% of cases and carries a median survival of 8-14 months without targeted therapy, due to its resistance to standard chemotherapies. Tagraxofusp-erzs, a CD123-directed cytotoxin conjugate, was approved by the FDA in 2018 for adults and pediatric patients aged 2 years and older with BPDCN, offering a first-line option with complete remission rates of 70-90% in treatment-naïve cases, though capillary leak syndrome remains a key toxicity. In the 2020s, real-world data confirmed tagraxofusp's efficacy in relapsed/refractory settings, with overall response rates exceeding 80% when combined with allogeneic stem cell transplantation for consolidation.^[75]^[76] Recent 2025 investigations into COVID-19 long-term effects highlight altered DC kinetics, with persistent pDC deficiencies and hyperactivation contributing to prolonged immune dysregulation in post-acute sequelae (PASC). Studies in animal models and human cohorts show persistent alterations in DC function, including sustained IFN-I production, contributing to PASC symptoms like fatigue and cognitive impairment. Longitudinal analyses reveal that severe SARS-CoV-2 infection impairs DC recovery, with reduced circulating cDC numbers and exhausted pDC IFN responses persisting beyond one year, underscoring DCs' role in chronic inflammation and vulnerability to secondary infections.^[77]^[78]

Comparative biology

Dendritic cells in non-human animals

Dendritic cells (DCs) in mice serve as a primary model for studying DC biology due to their well-characterized subsets and functional parallels to human DCs. The mouse CD8α+ conventional DCs (cDCs) are functionally equivalent to human cDC1, both specializing in cross-presentation of antigens to CD8+ T cells and expressing markers like XCR1.^[79]^[80] This equivalence has facilitated extensive research into DC ontogeny and antigen processing in mice, where CD8α+ DCs originate from bone marrow precursors dependent on transcription factors such as IRF8.^[81] Zebrafish provide a valuable non-mammalian model for investigating DC development, leveraging their optical transparency and genetic tractability for in vivo imaging of immune cell ontogeny. Recent studies have identified two distinct waves of DC development in zebrafish: an embryonic wave from the aorta-gonad-mesonephros region and an adult wave from hematopoietic niches, with distinct Flt3 dependencies.^[82] Zebrafish DCs express batf3, a gene critical for mammalian cDC1 development, highlighting conserved regulatory pathways.^[83] In veterinary medicine, DCs in livestock species like cattle are key targets for improving vaccine efficacy against economically significant diseases. Bovine skin DCs, which traffic antigens via afferent lymphatics to lymph nodes, have been studied for their role in priming adaptive responses, informing adjuvant designs that enhance DC activation for vaccines against pathogens like foot-and-mouth disease.^[84]^[85] In aquaculture, fish DCs contribute to mucosal immunity in species such as rainbow trout, where they bridge innate and adaptive responses to bacterial and viral challenges, supporting the development of oral vaccines to boost disease resistance in farmed fish populations.^[86] Comparative analyses reveal species-specific differences in DC subsets, such as in avian species where conventional DCs are identified via markers like XCR1 and FLT3, but plasmacytoid DC (pDC) homologs remain poorly defined due to limited specific markers and unclear interferon-producing cell equivalents.^[88]^[89] Despite these variations, the IRF8 transcription factor pathway is evolutionarily conserved across vertebrates, regulating DC differentiation and function from teleosts to mammals.^[90]^[91] Non-primate models, including mice and zebrafish, are instrumental in elucidating DC ontogeny without ethical constraints of primate research, enabling fate-mapping of DC precursors and identification of regulatory networks.^[81]

Evolutionary aspects

Dendritic cell-like antigen-presenting cells trace their origins to invertebrates, where phagocytic hemocytes in insects and other species exhibit dendritic morphology and functions such as pathogen engulfment and immune signaling, serving as evolutionary precursors to vertebrate professional antigen-presenting cells (APCs).^[92] These ancient innate immune effectors, including coelomocytes in echinoderms and hemocytes in mollusks and crustaceans, perform phagocytosis and produce reactive oxygen species without adaptive immunity components.^[92] In vertebrates, dendritic cells (DCs) emerged concurrently with adaptive immunity in jawed vertebrates (gnathostomes) around 540 million years ago during the Cambrian explosion, coinciding with the development of lymphoid tissues like the thymus and spleen to support T-cell priming.^[93] Langerhans cells, a DC subset, may represent one of the earliest types, originating from yolk sac progenitors in ancient fish for skin defense and homeostasis.^[93] DC functions demonstrate remarkable conservation across vertebrates, with homologs of major histocompatibility complex (MHC) molecules and Toll-like receptors (TLRs) enabling antigen processing and pathogen sensing in basal groups like fish and amphibians.^[94] In teleost fish such as rainbow trout, DC-like cells isolated from hematopoietic tissues display tree-like morphology, high MHC class II expression, phagocytic activity, and cytokine production (e.g., IL-12p40), bridging innate and adaptive responses much like mammalian DCs.^[86] These cells respond to TLR ligands by upregulating activation markers like CD83, indicating conserved signaling pathways for immune initiation.^[86] In amphibians, epidermal Langerhans cells express Langerin/CD207, MHC II, and TLR2, showing morphological and immunohistochemical homology to LCs in higher vertebrates and facilitating antigen presentation in diverse habitats.^[95] Plasmacytoid DC (pDC)-like populations in teleosts contribute to type I interferon production against viruses, underscoring early specialization for antiviral defense.^[93] Evolutionary pressures from pathogen diversity have shaped DC adaptations, particularly in frontline tissues exposed to microbial threats, driving genetic changes that enhance antigen sampling and T-cell orchestration.^[96] In barrier sites like the lungs, DCs exhibit elevated adaptive evolution rates, reflecting selection for rapid responses to inhaled bacteria and viruses via pathways like IFN-γ signaling.^[96] Gene family expansions and positive selection in transcription factors further illustrate these dynamics; for instance, in bats, the interferon regulatory factor (IRF) family, including IRF4 and IRF5 expressed in DCs, shows signatures of selection (e.g., ω = 2.290 for IRF4) that bolster inflammatory and antiviral functions without overt pathology.^[97] Such adaptations allow DCs to balance tolerance and immunity amid varying pathogen loads across species. Genomic studies from 2025 highlight the linkage of DC-related genes to jawed vertebrate evolution, revealing diversification of nonclassical MHC class I (MHC-Ib) genes outside the core MHC locus, with expansions (e.g., up to 100 copies in some fish) supporting specialized lipid antigen presentation to innate-like T cells via DCs.^[98] These MHC-Ib lineages, conserved from sharks to mammals, enable cross-presentation in endolysosomes, a mechanism likely mediated by DCs for non-peptide antigens.^[98] Concurrently, neofunctionalization in the NF-κB family, particularly Rel, has refined DC cytokine regulation during gnathostome radiation, with mammal-specific promoter changes enhancing Rel-dependent IL-12 production to drive Th1/Th17 responses.^[99] These findings underscore how DC gene networks co-evolved with adaptive immunity to counter diverse threats.^[99]

References

[1]
Dendritic Cells - PMC - PubMed Central - NIH
Dendritic cells (DCs) are professional antigen presenting cells that inform the fight against invasive pathogens while enforcing tolerance to self and harmless ...
[2]
Review of Dendritic Cells, Their Role in Clinical Immunology, and ...
Dendritic cells (DCs) are cells derived from the hematopoietic stem cells (HSCs) of the bone marrow and form a widely distributed cellular system throughout ...
[3]
Dendritic cell migration in inflammation and immunity - Nature
Jul 23, 2021 · Dendritic cells (DCs) are the key link between innate immunity and adaptive immunity and play crucial roles in both the promotion of immune defense and the ...Dc Migration Routes And... · Signaling Transduction Of Dc... · Molecular Regulation Of Dc...
[4]
Dendritic cells: Immunological sentinels with a central role in health ...
Dendritic cells (DCs) are professional antigen-presenting cells that act as peripheral sentinels, essential regulators of the immune system, and stimulate ...
[5]
Dendritic Cells - The Impact of Food Bioactives on Health - NCBI - NIH
Dendritic cells (DCs) are immune system sentinels, stimulating responses against pathogens and maintaining homeostasis. They are found in most tissues and are ...
[6]
Human Dendritic Cells: Their Heterogeneity and Clinical Application ...
Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation.
[7]
[PDF] Ralph Steinman and the Discovery of Dendritic Cells - Nobel Prize
What Steinman and Cohn found in 1973 when they looked through a phase contrast microscope was a different cell (Steinman and Cohn, 1973). It had dendritic ...
[8]
Dendritic cells and the immune response - Lasker Foundation
Feb 27, 2021 · The story of how dendritic cells were discovered began in 1970 when Steinman joined the laboratory of the late Zanvil Cohn at The Rockefeller ...
[9]
The discovery of dendritic cells | Journal of Experimental Medicine
May 26, 2021 · An excerpt from Ralph Steinman's Harvey Lecture describing the discovery of dendritic cells.
[10]
Human dendritic cell subsets - PMC - NIH
In humans, all DCs express high levels of MHC class II (HLA-DR) and lack typical lineage markers CD3 (T cell), CD19/20 (B cell) and CD56 (natural killer cell).
[11]
Ralph M. Steinman – Facts - NobelPrize.org
Ralph Steinman discovered, in 1973, a new cell type that he called the dendritic cell. In cell culture experiments he demonstrated that dendritic cells can ...
[12]
Human dendritic cell subsets: an update - PMC - NIH
A number of computational flow cytometry tools have been developed to scale and represent high dimensional data such as FlowSOM, tSNE, oneSENSE2, 23 and ISOMAP.
[13]
Development of conventional dendritic cells: from common bone ...
Feb 15, 2017 · Here, we review cDC development from the distinct progenitors in the bone marrow through to the distinct cDC subsets found in barrier tissues.
[14]
Human dendritic cell subsets: An updated view of their ontogeny ...
Characteristics of human cDC1 cDC1 are found in peripheral tissues and in lymphoid organs. Analysis of mucosal tissues and associated draining LNs has ...
[15]
Plasmacytoid dendritic cell biology and its role in immune‐mediated ...
May 26, 2020 · Plasmacytoid dendritic cells (pDCs) are a unique subset of dendritic cells specialised in secreting high levels of type I interferons.
[16]
Plasmacytoid Dendritic Cells: Development, Regulation, and Function
Plasmacytoid dendritic cells (pDCs) are innate immune sentinels that play important roles in immunity to infection and autoimmunity.Missing: characteristics | Show results with:characteristics
[17]
Plasmacytoid dendritic cells: development, functions, and role in ...
Plasmacytoid dendritic cells (pDCs) are a specialized subset of DCs that links innate and adaptive immunity. They sense viral and bacterial pathogens.
[18]
https://pmc.ncbi.nlm.nih.gov/articles/PMC6342491/
[19]
Dendritic cell subsets in cancer immunity and tumor antigen sensing
Mar 22, 2023 · Inflammatory DCs (bona fide DC3s) were identified in tumor ascites from patients with breast and ovarian cancer [20]. These cells can induce CD4 ...
[20]
Human in vivo-generated monocyte-derived dendritic cells and ...
Jul 2, 2018 · Human mo-DCs generated in vitro from monocytes cultured with GM-CSF and IL-4 can cross-present, and have long been used as a model to ...
[21]
Cytokine-armed dendritic cell progenitors for antigen-agnostic ...
Nov 23, 2023 · We present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 and FLT3L.
[22]
Engineering dendritic cell vaccines to improve cancer immunotherapy
Nov 27, 2019 · MoDCs generated ex vivo have been tested extensively in vaccination studies, which demonstrated their capacity to cross-prime T cells and ...
[23]
RARα supports the development of Langerhans cells and langerin ...
Sep 25, 2018 · Langerhans cells (LCs) are the prototype dendritic cells that reside specifically in the epidermis. At steady state, LCs are the only MHC-II- ...
[24]
Extricating human tumour immune alterations from tissue inflammation
May 11, 2022 · Single-cell analysis of human mononuclear phagocytes reveals subset-defining markers and identifies circulating inflammatory dendritic cells.
[25]
Ontogeny and Function of Dendritic Cells and Their Subsets in the ...
This review discusses major advances in our understanding of the regulation of DC lineage commitment, differentiation, diversification, and function in situ.
[26]
Human dendritic cell subsets and function in health and disease
Human DC arise from CD34+ haematopoietic precursors in the bone marrow that develop into monocyte-DC progenitors with the capacity to develop into monocytes, or ...
[27]
Dendritic Cell Lineage Potential in Human Early Hematopoietic ...
Jul 18, 2017 · Helft et al. show that multipotent lymphoid progenitors (MLPs) in humans are more efficient producers of CD141 + DNGR-1 + cDC1s than CMPs.
[28]
Dendritic Cell Development – History, Advances, and Open Questions
This review highlights studies of DC development—from the discovery of DCs as glass-adherent antigen presenting cells to the debate and resolution of their ...
[29]
Transcription Factor Networks in Dendritic Cell Development - PMC
This review summarizes the important cytokines and transcription factors required for differentiation of the DC lineage as well as further diversification into ...2. Unique Functions And... · 6. Transcription Factors... · 8. Gene Expression Analysis...<|control11|><|separator|>
[30]
Mechanisms and Consequences of Dendritic Cell Migration - PMC
DCs express specific adhesion molecules and maturation-dependent chemoattractant receptors that allow them to respond to a variety of ligands (Sozzani et al., ...
[31]
https://pmc.ncbi.nlm.nih.gov/articles/PMC4010935/
[32]
EBI1/CCR7 is a new member of dendritic cell chemokine receptor that is up-regulated upon maturation - PubMed
### Summary of Abstract and Key Findings on DC Maturation and CCR7 Upregulation
[33]
https://doi.org/10.1016/j.cell.2010.01.022
[34]
Dendritic cell homeostasis | Blood | American Society of Hematology
Apr 9, 2009 · Thus, the lifespan of differentiated pDCs in the spleen and LN is very short and continuous replacement via blood is essential.
[35]
Dendritic cell homeostasis - PMC - PubMed Central - NIH
Steady-state DC half-lives account for days to up to a few weeks, and they need to be replaced via proliferating hematopoietic progenitors, monocytes, or tissue ...
[36]
Plasmacytoid dendritic cells are short-lived - Nature
Apr 26, 2016 · They are thought to have a longer lifespan than conventional DCs (cDCs), largely based on a slower rate of BrdU labeling by splenic pDCs.
[37]
The lifespan and kinetics of human dendritic cell subsets and their ...
Oct 17, 2024 · Lubin, Patel, Mackerodt, and colleagues define the circulating lifespan of conventional human dendritic cells (cDC) at steady state.
[38]
Prosurvival Bcl-2 family members reveal a distinct apoptotic identity ...
Dendritic cell subsets differ in their expression of antiapoptotic BCL-2 family ... Classical Flt3L-dependent dendritic cells control immunity to protein vaccine.
[39]
The ins and outs of MHC class II-mediated antigen processing and ...
In this Review, we describe our current knowledge of the mechanisms of uptake and processing of antigens, the intracellular formation of peptide–MHC class II ...
[40]
Cathepsin S Controls the Trafficking and Maturation of Mhc Class II ...
I. Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell. 93. 1998. 1135. 1145. [PubMed].
[41]
Current Concepts of Antigen Cross-Presentation - PMC - NIH
Although substantial evidence points out that some antigens indeed can be cross-presented independent of proteasomal degradation and TAP-mediated peptide ...
[42]
Current Concepts of Antigen Cross-Presentation - Frontiers
Dendritic cells have the ability to efficiently present internalized antigens on major histocompatibility complex (MHC) I molecules.
[43]
The B7/BB1 antigen provides one of several costimulatory signals ...
The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro.
[44]
Costimulation via lymphocyte function-associated antigen 1 ... - PNAS
CD28 molecules are the best-characterized costimulatory receptors on T cells. ... molecules such as ICAM-1 and/or B7.2 were used to present peptide to class ...
[45]
Proteasomal degradation within endocytic organelles mediates ...
Jul 4, 2019 · Thus, phagosomal/endosomal binding of peptides locally generated by proteasomes allows cross‐presentation to generate MHC‐I‐peptide complexes ...Missing: cDC1 | Show results with:cDC1
[46]
Recent progress in type 1 classical dendritic cell cross-presentation
Jun 3, 2023 · Type 1 classical dendritic cells (cDC1s) have emerged as the major antigen-presenting cell performing cross-presentation (XP) in vivo, ...
[47]
https://www.embopress.org/doi/10.15252/embj.201899266
[48]
https://pubmed.ncbi.nlm.nih.gov/37276818/
[49]
Dendritic cells and cytokines in human inflammatory and ...
Dendritic cells (DCs) produce cytokines and are susceptible to cytokine-mediated activation. Thus, interaction of resting immature DCs with TLR ligands, ...
[50]
CCL19 and CCR7 Expression, Signaling Pathways, and Adjuvant ...
CCL19 is secreted by mature dendritic cells (mDCs), while CCL21 is secreted from the endothelium of afferent lymphatic vessels (this has been shown in mice, ...Introduction · Decreased CCR7 Expression... · CCR7 Is Required for the...
[51]
Pivotal Role of Dendritic Cell–derived CXCL10 in the Retention of T ...
Hepatic LN DCs preferentially produced CXCL10 to attract 5′-bromo-2′-deoxyuridine (BrdU)+CD4+ T cells and form clusters with IFN-γ–producing CD4+ T cells by day ...
[52]
Chemokine and chemotactic signals in dendritic cell migration - PMC
Mar 21, 2018 · CCL21 is important for directing DCs toward and along lymphatic vessels while CCL19 is involved, together with CCL21, in DC migration within ...
[53]
Tolerogenic IDO+ Dendritic Cells Are Induced by PD-1-Expressing ...
Here, we show that direct cell contact between immature monocyte-derived DCs (iDCs) and MC bends DCs toward tolerance induction. DCs that had direct contact ...
[54]
Tolerance through Education: How Tolerogenic Dendritic Cells ...
Tolerogenic DCs also alter T cell responses by modulation of metabolic parameters for example by the release of IDO and the induction of heme oxygenase-1 (HO-1) ...
[55]
Tolerogenic dendritic cells and their role in transplantation - PMC
DC are considered to play crucial roles in directing the alloimmune response towards transplant tolerance or rejection.<|control11|><|separator|>
[56]
Immunotherapy with myeloid cells for tolerance induction - PMC
Vitamin D3 A possible explanation for this is that activation of VD3 receptor reprograms dendritic cell maturation to differentiate them into tolerogenic cells ...
[57]
Dendritic cells as inducers of peripheral tolerance - PMC
In the periphery dendritic cells (DCs) play a critical tolerogenic role, extending the maintenance of immune homeostasis and blocking autoimmune responses.
[58]
The importance of dendritic cells in maintaining immune tolerance
Mar 15, 2018 · In the absence of inflammation, DCs can present self-antigens to T cells, providing transient T cell activation that can lead to either anergy ...
[59]
Mechanisms of Tolerance Induction by Dendritic Cells In Vivo - PMC
Furthermore, to eliminate autoreactive T cells that have escaped thymic deletion, DCs also induce immune tolerance in the periphery through various mechanisms.
[60]
The role of CD40 and CD40L in Dendritic Cells - PMC
In this review, we focus on the function of CD40-CD40L (CD154) interactions in the regulation of dendritic cell (DC) - T cell and DC-B cell cross-talk.
[61]
Molecular mechanism and function of CD40/CD40L engagement in ...
Overall, the impact of CD40 signaling 'licenses' DCs to mature and achieve all of the necessary characteristics to effectively trigger T-cell activation and ...
[62]
The Role of Dendritic Cell Subsets and Innate Immunity in ... - Frontiers
During inflammation (right panel), cDCs mature and can stimulate effector T cell responses, including Th1 and Th17 cells often associated with autoimmune ...
[63]
https://pmc.ncbi.nlm.nih.gov/articles/PMC3826168/
[64]
The role of tolerogenic dendritic cells in systematic lupus ...
Several attempts show the efficiency of tolDC as a suitable treatment in various autoimmune diseases, such as type 1 diabetes (T1D), rheumatoid arthritis (RA), ...
[65]
Unlocking the secrets of NPSLE: the role of dendritic cell ... - Frontiers
Sep 29, 2024 · Recent research has demonstrated the crucial involvement of dendritic cells (DCs) in developing SLE. The activation and dysfunction of DCs have ...
[66]
Dendritic Cell Subsets in Type 1 Diabetes: Friend or Foe? - Frontiers
Islet CD11b DC are relatively poor at presenting antigen under steady state conditions but they accumulate as inflammation increases and become more mature.
[67]
Dendritic cells in multiple sclerosis lesions: maturation stage, myelin ...
The most common finding was the presence of cells expressing DC-SIGN and containing myelin components in the perivascular cuffs of early active and chronic ( ...Missing: breakdown | Show results with:breakdown
[68]
Rapamycin Conditioning of Dendritic Cells Differentiated from ...
Given the role played by dendritic cells (DCs) in the establishment of immunological tolerance, we have proposed that DC, rendered tolerogenic during their ...
[69]
IRF8 Mutations and Human Dendritic-Cell Immunodeficiency | NEJM
### Summary of IRF8 Mutations and Their Link to Dendritic Cell Deficiency and Autoinflammatory/Autoimmune Aspects
[70]
the human equivalent of mouse CD8+ dendritic cells - PMC - NIH
New data now reveals the likely human equivalent of the mouse DC subset specialized in cross-presentation.
[71]
CD8α+ dendritic cells potentiate antitumor and immune activities ...
Jan 3, 2023 · Here, we report the effectiveness of mouse CD8α+ DCs derived from bone marrow hematopoietic stem cells (BM-HSCs), equivalent to human CD141+ DCs ...
[72]
Genetic models of human and mouse dendritic cell development ...
cDC1 and cDC2 subsets are functionally and transcriptionally more similar to each other than to pDCs43.
[73]
Dendritic cells in developing and adult zebrafish arise from different ...
Feb 17, 2025 · Our study reveals the presence of two distinct waves of DC development in zebrafish, each with unique origins and developmental controls.
[74]
A single-cell transcriptomic atlas reveals resident dendritic ... - eLife
Jan 9, 2024 · Notably, zebrafish DC-like cells rely on batf3, a gene essential for the development of conventional DC1 in the mouse. Using specific ...
[75]
Role of dendritic cells in the adaptive immune response of cattle
Aug 28, 2024 · The group has used a surgical cannulation model to examine the nature of dendritic cells trafficking from the skin in afferent lymphatic vessels ...<|separator|>
[76]
Transcriptomic profiling of bovine blood dendritic cells and ...
Jun 27, 2020 · This in-depth analysis of ligand responsiveness is essential for the rational design of vaccine adjuvants in cattle, and provides a solid basis ...Regulation Of Ifn Genes And... · Isolation Of Bovine Pbmc · Stimulation With Tlr Ligands
[77]
Functional Identification of Dendritic Cells in the Teleost Model ...
Jawed fishes are the earliest vertebrates capable of adaptive immunity (involving MHC, BCR and TCR), and the molecular machinery necessary for antigen ...
[78]
Main Components of Fish Immunity: An Overview of the Fish ... - MDPI
The main cellular constituents of the fish immune system are macrophages, granulocytes, dendritic cells, NK cells, and cytotoxic T cells.
[79]
Development of novel reagents to chicken FLT3, XCR1 and CSF2R ...
Nov 12, 2021 · We have developed tools to specifically identify chicken conventional dendritic cells (cDCs). Chicken cDCs are express high levels of FLT3 ...
[80]
Dendritic cell harmonised immunity to poultry pathogens; a review
Jul 3, 2017 · The phenotype of avian DCs is less understood because of a lack of specific markers but these can be cultured and activated by LPS. These ...
[81]
Investigating Evolutionary Conservation of Dendritic Cell Subset ...
Dendritic cells (DCs) were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T-cell activation.
[82]
Differential IRF8 Transcription Factor Requirement Defines Two ...
Aug 18, 2020 · The formation of mammalian dendritic cells (DCs) is controlled by multiple hematopoietic transcription factors, including IRF8.
[83]
Differentiation-inducing factor-1 inhibits dendritic cell function by ...
Aug 28, 2025 · With regard to innate immunity, DIF-1 reportedly inhibits attacin production and the proliferation of macrophage-like Drosophila S2 cells [22].
[84]
Stem Cells and Innate Immunity in Aquatic Invertebrates
They have a dendritic-like shape and phagocytic activity and their specification is determined by the transcription factor foxF-1 (54). Data support a ...
[85]
Dendritic Cells in the Immune System—History, Lineages, Tissues ...
This review seeks to provide a conceptual framework for understanding dendritic cells (DCs). It focuses mainly on DCs of mice, and to a lesser extent humans.
[86]
Conservation of Toll-Like Receptor Signaling Pathways in Teleost Fish
In this study, we establish evolutionary conservation in teleost fish of key components of the TLR-signaling pathway that act as switches for differential gene ...
[87]
Immunohistochemical Characterization of Langerhans Cells in the ...
Mar 23, 2024 · In conclusion, the amphibian dendritic cells are morphologically and immunohistochemically homologous to the LCs of all vertebrates so they can ...1. Introduction · 2. Materials And Methods · 2.4. Confocal...
[88]
Adaptation in human immune cells residing in tissues at the frontline ...
Nov 28, 2024 · Human immune cells are under constant evolutionary pressure, primarily through their role as first line of defence against pathogens.
[89]
Uncovering selection pressures on the IRF gene family in bats ...
Jan 7, 2025 · Recent research has explored the complex mechanisms underlying the balance between bats' antiviral defenses and their pathological responses.<|separator|>
[90]
Evolutionary Perspective of Nonclassical MHC Class I and Innate ...
Oct 14, 2025 · In all jawed vertebrates, MHC-Ia genes are highly polymorphic and located in the MHC genomic locus proper, which includes a plethora of genes ( ...
[91]
Stepwise neofunctionalization of the NF-κB family member Rel ...
Apr 30, 2025 · Comparison of the Il12b promoter provides a glimpse of possible broad transitions in Il12b regulatory strategies during vertebrate evolution; ...