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Monocyte

Monocytes are a type of white blood cell belonging to the mononuclear phagocyte system, originating from hematopoietic stem cells in the bone marrow and circulating in the peripheral blood, where they typically comprise 2–8% of total leukocytes.^[1] They serve as precursors to macrophages and dendritic cells, migrating into tissues to differentiate and contribute to the innate immune response by combating infections, regulating inflammation, and maintaining cellular homeostasis.^[2]^[3] Morphologically, monocytes are the largest normal leukocytes, measuring 12–20 μm in diameter, with a characteristic large, kidney-shaped or horseshoe-shaped nucleus that occupies much of the cell, and pale blue-gray cytoplasm containing fine azurophilic granules and vacuoles.^[4] In humans, circulating monocytes are heterogeneous and classified into three major subsets based on differential expression of the surface markers CD14 and CD16: classical monocytes (CD14⁺⁺CD16⁻, approximately 80–90% of total monocytes, primarily phagocytic and inflammatory), intermediate monocytes (CD14⁺⁺CD16⁺, 5–10%, with enhanced antigen presentation and cytokine production), and non-classical monocytes (CD14⁺CD16⁺⁺, 5–10%, involved in vascular patrolling and tissue surveillance).^[5] These subsets exhibit distinct gene expression profiles, sizes, nuclear shapes, and functional roles, reflecting their specialized contributions to immunity.^[6] Functionally, monocytes bridge innate and adaptive immunity through phagocytosis of pathogens and debris, antigen presentation to T cells via MHC molecules, secretion of pro- and anti-inflammatory cytokines (such as TNF-α, IL-1, and IL-10), and chemokine production to recruit other immune cells during infection, injury, or chronic inflammation.^[7]^[2] Upon tissue infiltration, they differentiate into macrophages for long-term phagocytosis and tissue remodeling or into dendritic cells for antigen processing and immune activation, playing critical roles in host defense against bacteria, viruses, and parasites, as well as in pathological conditions like atherosclerosis, cancer progression, and autoimmune diseases.^[8]^[9]

Morphology and Structure

Physical Characteristics

Monocytes are the largest leukocytes in human peripheral blood, with a typical diameter of 12-20 μm, approximately twice the size of erythrocytes. They constitute 2-8% of the total white blood cell count, corresponding to an absolute monocyte count of 0.2-0.8 × 10⁹/L in healthy adults. These cells circulate in the peripheral blood for 1-3 days prior to migrating into tissues. Morphologically, monocytes display an amoeboid shape characterized by irregular outlines and pseudopodia-like extensions. The nucleus is prominent, often indented, horseshoe-, or kidney-bean-shaped, and occupies up to half or more of the cell volume, with a lacy chromatin pattern. The cytoplasm is agranular overall but contains fine azurophilic granules; under Wright-Giemsa staining, it appears pale blue-gray, distinguishing monocytes from granulocytes. In other species, such as mice, monocytes exhibit similar morphological features but are slightly smaller, with diameters typically ranging from 10-15 μm.

Cellular Components

Monocytes possess an eccentric nucleus that typically exhibits a horseshoe- or band-shaped morphology with dispersed, loosely packed chromatin, often appearing kidney-shaped in blood smears due to its bilobed structure.^[10] This nuclear configuration, surrounded by a thin rim of cytoplasm, facilitates the cell's amoeboid movement and phagocytic capabilities without compromising structural integrity.^[11] The cytoplasm of monocytes is abundant and contains key organelles essential for their metabolic and immune functions, including numerous mitochondria for energy production, rough endoplasmic reticulum for protein synthesis, a prominent Golgi apparatus for processing and packaging, and lysosomes for degradative processes.^[11] Unlike granulocytes, monocytes lack specific granules but feature vacuoles that support phagocytosis by enabling the engulfment and initial containment of pathogens or debris. These components collectively provide the machinery for rapid response to inflammatory signals. On their surface, monocytes express characteristic markers such as CD14, a lipopolysaccharide-binding protein that identifies classical monocytes, CD11b (an integrin subunit involved in adhesion), and HLA-DR (a major histocompatibility complex class II molecule for antigen presentation), which are routinely used for identification via flow cytometry.^[5] Additionally, adhesion molecules like LFA-1 (CD11a/CD18) and VLA-4 (CD49d/CD29) mediate interactions with endothelial cells and extracellular matrix, crucial for tissue infiltration.^[12] Cytoskeletal elements in monocytes include dynamic actin filaments and microtubules, which orchestrate cell motility, pseudopod extension for crawling, and intracellular transport of vesicles during migration.^[13] Actin polymerization drives the formation of lamellipodia and filopodia at the leading edge, while microtubules provide directional guidance and structural support for organelle positioning.^[14] Metabolically, monocytes exhibit high glycolytic activity to meet rapid energy demands during activation and circulation, particularly in classical subsets that prioritize quick inflammatory responses over oxidative phosphorylation.^[15] They also rely on fatty acid oxidation as an alternative pathway, especially under glucose-limiting conditions or during sustained function, allowing metabolic flexibility in hypoxic or nutrient-variable environments.^[16]

Development and Lifecycle

Hematopoietic Origin

Monocytes originate in the bone marrow through a tightly regulated process of hematopoiesis, deriving from hematopoietic stem cells that progress through committed progenitors. Specifically, they arise from common myeloid progenitors (CMPs), which differentiate into monoblasts and subsequently promonocytes before maturing into circulating monocytes.^[17] This lineage commitment occurs within the bone marrow microenvironment, where CMPs give rise to granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs), marking the initial stages of monopoiesis.^[18] The development of monocytes is governed by key transcription factors that orchestrate gene expression for myeloid differentiation. PU.1 (encoded by SPI1) acts as a master regulator, promoting monocyte lineage specification while suppressing alternative pathways, often in balance with factors like C/EBPα, which drives early myeloid commitment and granulocyte-monocyte branching.^[19] Additionally, IRF8 (also known as ICSBP) is essential for monopoiesis, enabling the transition from progenitors to monocytes by activating monocyte-specific genes and inhibiting granulocytic differentiation.^[20] These factors interact dynamically to ensure precise control over cell fate decisions during hematopoiesis. In healthy adult humans, the bone marrow produces approximately 5 × 10^9 monocytes per day to maintain steady-state circulation, a process stimulated primarily by cytokines such as macrophage colony-stimulating factor (M-CSF, or CSF1) and granulocyte-macrophage colony-stimulating factor (GM-CSF).^[21] M-CSF supports the survival, proliferation, and differentiation of monocyte progenitors, while GM-CSF enhances myeloid output under homeostatic and inflammatory conditions.^[22] This production is embedded within the bone marrow niche, where hematopoietic progenitors interact with stromal cells, endothelial components, and the extracellular matrix to receive essential signals like CXCL12 and SCF, fostering an supportive environment for monopoiesis.^[23] The hematopoietic origin of monocytes shows strong conservation across species, with a comparable pathway observed in mice. In murine models, early monocyte progenitors express Ly6C as a distinguishing marker, facilitating identification of inflammatory (Ly6C^high) subsets during bone marrow differentiation, akin to human classical monocytes.^[18]

Maturation and Tissue Migration

Mature monocytes exit the bone marrow and enter the bloodstream, where they constitute approximately 2-10% of circulating leukocytes in humans.^[2] Upon release, these cells maintain a short circulatory half-life of 1-3 days under steady-state conditions, after which they either differentiate further or are cleared.^[24] This transient presence in the blood allows monocytes to serve as a rapid reservoir for immune responses, with their numbers and subsets regulated by homeostatic signals to prevent excessive accumulation.^[25] Recruitment of circulating monocytes to inflamed or infected tissues is primarily driven by chemotaxis, where gradients of chemokines such as CCL2 (also known as monocyte chemoattractant protein-1, or MCP-1) bind to the CCR2 receptor on the monocyte surface.^[26] This interaction promotes firm adhesion to the vascular endothelium and subsequent diapedesis, enabling monocytes to cross the endothelial barrier and infiltrate extravascular spaces.^[27] The process is highly responsive to local inflammatory cues, ensuring targeted migration without widespread dissemination. Upon entering tissues, monocytes encounter activation signals including Toll-like receptor (TLR) ligands from pathogens and cytokines from resident immune cells, which trigger intracellular signaling cascades such as the NF-κB pathway to induce transcriptional reprogramming.^[28] This activation enhances monocyte survival and motility while preparing them for differentiation, often within hours of tissue entry.^[29] In various organs, including the spleen, liver, and lungs, recruited monocytes differentiate into long-lived tissue-resident macrophages or dendritic cells, adopting organ-specific phenotypes that support local immune surveillance and homeostasis.^[30] For instance, in the spleen, monocytes contribute to red pulp macrophage populations, while in the lungs, they replenish alveolar macrophages.^[31] This conversion is influenced by tissue-derived factors, allowing monocytes to integrate into the resident myeloid network. If not recruited to tissues, circulating monocytes are subject to programmed cell death via apoptosis, a regulatory mechanism that maintains population balance and prevents chronic inflammation.^[32] Anti-apoptotic proteins such as Bcl-2 play a critical role in modulating this process, with enforced Bcl-2 expression extending monocyte survival and supporting differentiation into macrophages.^[33] This apoptotic control ensures that only appropriately activated monocytes persist in peripheral compartments.

Subpopulations and Heterogeneity

Human Subtypes

Human monocytes are classified into three primary subpopulations based on the differential expression of surface markers CD14 and CD16: classical (CD14⁺⁺CD16^-), intermediate (CD14⁺⁺CD16⁺), and non-classical (CD14⁺CD16⁺⁺).^[34] This classification, established through flow cytometry and transcriptomic analyses, reflects their distinct developmental origins and phenotypic heterogeneity.^[35] Classical monocytes constitute the majority of circulating monocytes, comprising approximately 80-90% of the total pool, and are continuously produced from bone marrow progenitors.^[36] They exhibit high expression of CD14, a lipopolysaccharide co-receptor, and lack CD16, distinguishing them from the other subsets.^[37] Intermediate monocytes represent 5-10% of the population and display intermediate levels of both CD14 and CD16, bridging the classical and non-classical subsets in marker expression.^[5] Non-classical monocytes, also 5-10% of the total, are characterized by low CD14 and high CD16 expression; they derive sequentially from classical monocytes through an intermediate stage in steady-state conditions.^[36] Further subclassification employs additional surface markers such as CD62L (L-selectin), which is highly expressed on classical monocytes but downregulated on non-classical ones, aiding in their distinction during migration.^[38] CX3CR1, the fractalkine receptor, shows low expression on classical and intermediate subsets but is upregulated on non-classical monocytes, reflecting differences in chemokine responsiveness.^[39] The carbohydrate antigen 6-sulfo LacNAc (SLAN) serves as a specific marker for a subset of non-classical monocytes, enabling refined identification beyond CD14 and CD16.^[40] In terms of proportions and dynamics, classical monocytes have the shortest circulating lifespan of approximately 1 day, intermediate monocytes ~4 days, and non-classical monocytes ~7 days.^[36] Recent studies have revealed emerging epigenetic differences among these subtypes in the context of aging, with shifts in subset fractions correlating to epigenetic clock accelerations and age-related health outcomes.^[41]

Murine Subtypes

In mice, monocytes are primarily classified into two major subsets based on surface marker expression: inflammatory monocytes characterized by high Ly6C (Ly6C^high), CCR2⁺, and low CX3CR1 (CX3CR1^low), and patrolling monocytes marked by low Ly6C (Ly6C^low), CCR2^-, and high CX3CR1 (CX3CR1^high).^[24]^[42] Inflammatory monocytes, analogous to human classical monocytes, are rapidly recruited to sites of inflammation via CCR2-mediated chemotaxis in response to chemokines like CCL2, where they exhibit potent proinflammatory functions including high production of interleukin-1β (IL-1β).^[42]^[43]^[44] These cells originate from bone marrow progenitors and constitute the majority of circulating monocytes, typically comprising approximately 80-90% of blood monocytes under steady-state conditions, though proportions can shift toward higher levels during infection or inflammation.^[45]^[46] Patrolling monocytes, similar to human non-classical monocytes, continuously survey the vascular endothelium without eliciting strong inflammatory responses; they efficiently clear cellular debris, damaged endothelial cells, and microbial particles through CX3CR1-dependent crawling and efferocytosis, contributing to vascular homeostasis and early containment of pathogens.^[24]^[47]^[48] Murine monocyte development occurs in distinct waves, with Ly6C^high monocytes exiting the bone marrow into the bloodstream before a subset undergoes conversion to Ly6C^low monocytes primarily in the spleen through downregulation of Ly6C and upregulation of CX3CR1, driven by factors such as the transcription factor C/EBPβ; unlike in humans, mice lack a direct intermediate monocyte equivalent during this process.^[49]^[50] These subtypes serve as valuable models for studying human monocyte biology due to conserved functional parallels, and murine systems enable precise experimental manipulation.^[51] Knockout models, such as CCR2^-/- mice, demonstrate impaired recruitment of Ly6C^high monocytes to inflammatory sites, highlighting CCR2's critical role in mobilization and underscoring the utility of these models for dissecting recruitment mechanisms.^[52]^[53] Recent research has identified tissue-specific monocyte heterogeneity, addressing gaps in understanding beyond circulation.^[54]

Physiological Functions

Innate Immune Roles

Monocytes serve as key effectors in the innate immune system by recognizing and engulfing pathogens, apoptotic cells, and cellular debris through phagocytosis, a process mediated by pattern recognition receptors (PRRs) such as Toll-like receptor 4 (TLR4). TLR4, in complex with CD14 and MD-2, binds lipopolysaccharide (LPS) from Gram-negative bacteria, triggering receptor endocytosis into phagosomes where it activates inflammatory signaling pathways, including NF-κB and MAPK, to enhance pathogen clearance.^[55] This phagocytic activity not only internalizes threats but also couples with inflammasome activation, such as caspase-4 and caspase-5 sensing cytosolic LPS, amplifying antimicrobial responses in monocytes.^[55] In response to pathogen-associated molecular patterns (PAMPs), monocytes secrete a range of cytokines to orchestrate inflammation and immune modulation. Pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) are rapidly produced via TLR signaling, activating NF-κB and JAK-STAT pathways to recruit additional immune cells and promote systemic responses.^[56] Conversely, interleukin-10 (IL-10) is released by monocytes to dampen excessive inflammation, inhibiting TNF-α and IL-6 production and facilitating resolution of the acute phase.^[56] These cytokine profiles enable monocytes to balance pathogen elimination with prevention of tissue damage. Monocytes also bridge innate and adaptive immunity through antigen presentation, expressing major histocompatibility complex class II (MHC II) molecules to process and display exogenous antigens to CD4+ T cells. Among monocyte subsets, intermediate monocytes exhibit the highest constitutive MHC II expression (HLA-DR, -DP, -DQ) and lowest CLIP:MHCII ratios, indicating efficient peptide loading and T-cell priming capabilities.^[57] Cytokines like interferon-gamma (IFNγ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulate MHC II on classical monocytes, enhancing their role in initiating adaptive responses during infection.^[57] Beyond direct antimicrobial actions, monocytes contribute to tissue repair by clearing damaged extracellular matrix (ECM) components and promoting angiogenesis. Monocyte-derived macrophages secrete matrix metalloproteinases (MMPs) to degrade ECM, releasing sequestered growth factors and facilitating remodeling in injured tissues.^[58] They also produce vascular endothelial growth factor (VEGF), which stimulates endothelial cell proliferation and new vessel formation, essential for wound healing and regeneration.^[58] Monocyte subpopulations exhibit distinct innate immune roles, with classical monocytes (CD14++CD16-) specializing in rapid phagocytosis and pro-inflammatory cytokine release for acute responses, while non-classical monocytes (CD14+CD16++) patrol vasculature, maintaining homeostasis through anti-inflammatory IL-10 production and patrolling for early pathogen detection.^[35] Emerging evidence highlights monocyte extracellular traps (METs), web-like structures of DNA and antimicrobial proteins released upon stimulation by microbes like Escherichia coli or Candida albicans, which entrap and kill pathogens without compromising cell viability, providing an additional layer of defense.^[59]

Differentiation into Effector Cells

Upon entering tissues, monocytes undergo differentiation into specialized effector cells, primarily macrophages and dendritic cells, guided by local cytokine environments. Macrophage differentiation is primarily driven by macrophage colony-stimulating factor (M-CSF, also known as CSF-1), which promotes the transition from monocytes to unpolarized M0 macrophages.^[60] These M0 macrophages can then polarize into pro-inflammatory M1 phenotypes in response to interferon-gamma (IFN-γ) and lipopolysaccharide (LPS), enhancing antimicrobial and tumoricidal activities, or into anti-inflammatory M2 phenotypes under the influence of interleukin-4 (IL-4) or IL-13, supporting tissue repair and resolution of inflammation.^[61] This polarization is regulated by signaling pathways involving STAT1 for M1 and STAT6 for M2, ensuring adaptive responses to diverse pathological cues.^[61] Dendritic cell formation from monocytes occurs through exposure to granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with IL-4, generating immature dendritic cells (DCs) that express high levels of MHC class II and co-stimulatory molecules.^[62] These immature DCs acquire antigen-presenting capabilities and mature upon Toll-like receptor (TLR) stimulation, such as by pathogen-associated molecular patterns, leading to upregulation of CD80, CD86, and CD83 for efficient T-cell priming.^[63] This process enables monocytes to bridge innate and adaptive immunity by facilitating antigen cross-presentation to CD8+ T cells.^[64] Post-tissue migration, differentiation timelines typically span 24-72 hours, during which monocytes commit to effector fates through epigenetic reprogramming, including histone modifications like H3K27me3 methylation that stabilize M2-like states.^[65] Organ-specific adaptations further tailor these cells; for instance, monocyte-derived alveolar macrophages in the lungs adopt surfactant clearance functions,^[66] while Kupffer cells in the liver specialize in scavenging gut-derived endotoxins.^[67] Recent findings highlight monocyte-to-osteoclast differentiation in bone remodeling, where RANKL and M-CSF drive fusion into multinucleated osteoclasts for calcium homeostasis, with disruptions linked to inflammatory bone loss in 2025 studies on spondyloarthritis.^[68] Monocyte-derived effector cells exhibit limited plasticity, particularly in chronic inflammatory settings, where M1 macrophages can be reprogrammed toward M2 phenotypes via IL-4 signaling or metabolic shifts, allowing therapeutic modulation of fibrosis or autoimmunity.^[60] This reversibility underscores the dynamic nature of monocyte fates, influenced by persistent environmental signals post-initial differentiation.^[61]

Pathophysiology and Clinical Relevance

Disorders of Monocyte Counts

Monocytosis refers to an elevated absolute monocyte count in the peripheral blood, typically defined as greater than 0.8 × 10⁹/L (or 800/μL).^[69] This condition can be classified into reactive (non-neoplastic) and neoplastic types. Reactive monocytosis often arises from chronic infections such as tuberculosis (TB), autoimmune diseases like rheumatoid arthritis, or inflammatory states, where monocytes are recruited to sites of ongoing immune activation.^[70]^[71] Neoplastic monocytosis, in contrast, is associated with hematologic malignancies, including chronic myelogenous leukemia (CML), where clonal expansion of myeloid precursors leads to persistent elevation.^[71] Distinguishing between these types requires clinical correlation and further testing, such as bone marrow examination, to rule out underlying malignancy.^[72] Monocytopenia, conversely, is characterized by a reduced absolute monocyte count, generally below 0.2 × 10⁹/L (or 200/μL).^[73] Common causes include chemotherapy-induced myelosuppression, which temporarily impairs bone marrow production of monocytes alongside other leukocytes.^[74] Viral infections, particularly HIV, can also lead to monocytopenia through direct effects on hematopoietic cells or immune dysregulation.^[75] Additionally, genetic disorders such as GATA2 deficiency result in profound and persistent monocytopenia due to impaired transcription of genes essential for monocyte development, often presenting as part of MonoMAC syndrome.^[73]^[76] Monocyte counts are primarily measured through a complete blood count (CBC) with differential, which provides the absolute monocyte count as a standard component of routine hematologic evaluation.^[73] For confirmation, especially in cases of suspected subsets or clonal abnormalities, flow cytometry can be employed to quantify and characterize monocyte populations based on surface markers like CD14 and CD16.^[77] Ethnic variations influence baseline monocyte counts, with individuals of African descent typically exhibiting lower normal ranges compared to those of European ancestry, potentially affecting diagnostic thresholds in diverse populations.^[78]^[79] In terms of prognostic value, elevated monocyte counts (monocytosis) in patients with sepsis are associated with adverse outcomes, including higher mortality risk, as they reflect dysregulated inflammatory responses.^[80] Studies have also linked monocytopenia to increased severity and poorer prognosis in COVID-19, particularly in severe cases where monocyte depletion correlates with exaggerated cytokine storms and organ dysfunction.^[81]^[82]

Roles in Specific Diseases

In chronic inflammatory conditions, non-classical monocytes (CD14^low CD16^high) contribute to atherosclerosis by promoting endothelial dysfunction and vascular inflammation through increased adhesion to the arterial wall, facilitating plaque formation.^[83] These monocytes express high levels of CD16 and exhibit pro-atherogenic properties by secreting inflammatory mediators that exacerbate lipid accumulation and foam cell development in atherosclerotic lesions.^[83] In contrast, classical monocytes (CD14^high CD16^-) play a prominent role in rheumatoid arthritis (RA), where they infiltrate synovial tissues and drive joint inflammation via production of tumor necrosis factor-alpha (TNF-α), amplifying cytokine networks that sustain autoimmune responses.^[84] TNF-α blockade therapies, such as infliximab, reduce classical monocyte activation and numbers, underscoring their centrality in RA pathogenesis.^[85] In cancer, monocytes differentiate into tumor-associated macrophages (TAMs) within the tumor microenvironment, often skewing toward an M2-like phenotype that suppresses anti-tumor immunity and promotes tumor growth, angiogenesis, and metastasis.^[86] This M2 skewing is driven by tumor-derived factors like IL-6 and leukemia inhibitory factor, which reprogram monocytes to produce immunosuppressive cytokines such as IL-10, impairing T-cell responses.^[87] Emerging research from 2024-2025 highlights monocyte-based chimeric antigen receptor (CAR) therapies, particularly CAR-macrophages engineered from patient-derived monocytes, which target solid tumors by enhancing phagocytosis of cancer cells and shifting the microenvironment toward anti-tumor M1 polarization.^[88] Preclinical models demonstrate that these CAR-monocyte derivatives improve efficacy against glioblastoma and other malignancies resistant to CAR-T cells.^[88] During infections, monocyte hyperactivation in sepsis leads to excessive cytokine release, contributing to the cytokine storm that drives multi-organ failure.^[89] Proinflammatory monocytes produce high levels of IL-6 and TNF-α in response to microbial stimuli, amplifying systemic inflammation and endothelial damage.^[90] Conversely, monocyte deficiencies, as seen in conditions like GATA2 deficiency or advanced HIV/AIDS, impair phagocytic clearance and increase susceptibility to opportunistic infections such as Pneumocystis jirovecii or Mycobacterium avium, due to reduced antimicrobial activity and T-cell support.^[91]^[92] In autoimmunity and neurodegeneration, monocytes infiltrate multiple sclerosis (MS) plaques, where proinflammatory subsets exacerbate demyelination by secreting matrix metalloproteinases and reactive oxygen species that breach the blood-brain barrier.^[93] In MS models, CCR2-dependent monocyte recruitment sustains chronic inflammation in active lesions.^[93] In Alzheimer's disease, circulating monocytes contribute to amyloid-beta (Aβ) clearance via phagocytosis, but impaired function in aging or disease states reduces Aβ uptake, allowing plaque accumulation; mutations like TREM2 R47H in monocytes further diminish this protective role.^[94]^[95] Therapeutic strategies targeting monocytes show promise in disease models. Monocyte depletion using agents like clodronate liposomes reduces inflammation and tissue damage in experimental autoimmune encephalomyelitis (a MS model) and traumatic brain injury by limiting pathogenic infiltration.^[96]^[97] In inflammatory bowel disease (IBD), CCR2 antagonists block Ly6C^high monocyte recruitment to the gut mucosa, alleviating colitis severity in murine models by decreasing macrophage accumulation and cytokine production.^[98] Recent 2024-2025 studies reveal emerging microbiome-monocyte interactions in IBD, where dysbiotic gut bacteria modulate monocyte differentiation toward proinflammatory states via short-chain fatty acid signaling, suggesting microbiota-targeted interventions to restore monocyte homeostasis.^[99]

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Occurrences and Functions of Ly6C hi and Ly6C lo Macrophages in ...
May 29, 2022 · In this review, we discuss the basic biology of Ly6C hi and Ly6C lo macrophages, including their origin, differentiation, and phenotypic switching.
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Monocytes and macrophages: Origin, homing, differentiation, and ...
Apr 30, 2024 · The Ly6Clo subset participates in patrolling, initial events of inflammation, and tissue repair. They express lower levels of CCR2 and higher ...
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The Ontogeny of Monocyte Subsets - Frontiers
Jul 16, 2019 · The conversion of Ly6Chi monocytes to Ly6C− monocytes is dependent on the transcription factor c/EBPβ, which is required for the survival of ...
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Triggering of NOD2 Receptor Converts Inflammatory Ly6Chigh into ...
Aug 22, 2017 · We demonstrate that triggering of the NOD2 receptor by muramyl dipeptide (MDP) converts inflammatory Ly6C high monocytes into patrolling Ly6C low monocytes.
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Murine Monocytes: Origins, Subsets, Fates, and Functions
The BM also harbors a rare population of Ly6C– monocytes that could derive from Ly6C+ monocytes or cMoPs, but the function of this subset is unknown. Ly6C+ ...
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Critical roles for CCR2 and MCP-3 in monocyte mobilization ... - JCI
Intravenous infusion of ex vivo–labeled WT or CCR2–/– bone marrow into WT recipient mice demonstrated that CCR2 is necessary for efficient monocyte recruitment ...
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004999 - CCR2- Strain Details - The Jackson Laboratory
Dec 24, 2024 · B6.129S4-Ccr2 tm1Ifc/J mice have defective monocyte recruitment, impacting immune responses, and are susceptible to some infections. They are ...
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Monocyte-driven inflamm-aging reduces intestinal barrier function in ...
Sep 30, 2024 · Beyond their potential role in inflamm-aging, age-associated changes in monocyte subsets may contribute to impaired intestinal barrier function.
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Insights into phagocytosis-coupled activation of Pattern Recognition ...
A soluble form of MD-2, which binds LPS in the TLR4 membrane complex, has been shown to opsonize Gram-negative bacteria and enhance their phagocytosis by ...
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Inflammatory responses and inflammation-associated diseases in ...
Stimuli activate inflammatory cells, such as macrophages and adipocytes, and induce production of inflammatory cytokines, such as IL-1β, IL-6, TNF-α, and ...
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The MHC class II antigen presentation pathway in human ...
Monocytes play a critical role in the innate and adaptive immune systems, performing phagocytosis, presenting antigen, and producing cytokines.
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Monocyte-endothelial cell interactions in vascular and tissue ...
... monocyte adhesion molecules (10). Therefore, monocytes are dynamic cellular components that can complete the functions of tissue-resident mononuclear ...
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Extracellular Trap by Blood Cells: Clinical Implications - PMC
Feb 29, 2020 · Monocyte extracellular traps. Monocytes are a group of multi-faceted blood cells which are circulating in peripheral blood and are able to ...
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Tissue macrophages: origin, heterogenity, biological functions ...
Mar 7, 2025 · ... cellular components ... Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases.<|control11|><|separator|>
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Macrophages in immunoregulation and therapeutics - Nature
May 22, 2023 · Macrophages are crucial in innate immunity by regulating several homeostatic and evolutionary host defense immune responses.
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Human monocytes undergo functional re-programming during ...
Feb 9, 2016 · In vitro cultures of human CD14+ monocytes with GM-CSF and IL-4 induces the differentiation of immature DCs, with characteristic marker ...
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Distinct metabolic states guide maturation of inflammatory and ...
Sep 2, 2022 · GM-CSF/IL4-induce rapid reprogramming of glycolytic monocytes and transient co-activation of mitochondrial pathways followed by TLR4-dependent ...
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Ezh2 emerges as an epigenetic checkpoint regulator during ... - Nature
Jul 25, 2023 · Epigenetic regulation of histone H3K27 methylation has recently emerged as a key step during alternative immunoregulatory M2-like macrophage ...
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Osteoclast development from peripheral blood monocytes is ...
May 30, 2025 · Osteoclast development from peripheral blood monocytes is reduced in patients with radiographic axial spondyloarthritis on biological therapy.
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Monocytosis - an overview | ScienceDirect Topics
Monocytosis has been defined as a sustained absolute increase in monocyte count greater than 800/mm3 to 1000/mm3 (Table 48.3). Transient monocytosis, relative ...
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Monocyte Disorders - Blood Disorders - Merck Manuals
An increased number of monocytes in the blood (monocytosis) occurs in response to chronic infections, in autoimmune disorders, in blood disorders, and in ...
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How I investigate monocytosis - Lynch - 2018 - Wiley Online Library
Jan 18, 2018 · Monocytosis is a common finding that is caused by a wide variety of neoplastic and non-neoplastic conditions. The adequate evaluation of ...
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Differential Diagnosis and Workup of Monocytosis - PubMed Central
Apr 20, 2021 · The normal absolute monocyte count ranges in adults ranges in between 0.2–0.8 × 109/L, with values varying significantly with age and sex.
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Monocytopenia - Hematology and Oncology - Merck Manuals
Monocytopenia is a reduction in blood monocyte count to < 200/mcL (< 0.2 × 10 9/L). Risk of certain infections is increased. It is diagnosed by complete ...Missing: definition threshold
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Monocytopenia - Hematology and Oncology - MSD Manuals
Mar 26, 2022 · Monocytopenia is a reduction in blood monocyte count to < 200/mcL (< 0.2 × 10 9/L). Risk of certain infections is increased.Missing: threshold | Show results with:threshold
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Real world data on the prognostic significance of monocytopenia in ...
Oct 26, 2022 · Monocytopenia can result from several conditions such as chemotherapy ... HIV infection, corticosteroid administration and in the MonoMAC ...Results · Monocytopenia In Patients... · Discussion<|control11|><|separator|>
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GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics ...
Feb 6, 2014 · Haploinsufficiency of the hematopoietic transcription factor GATA2 underlies monocytopenia and mycobacterial infections; dendritic cell, ...
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Multicenter validation of the flow measurement of classical monocyte ...
Nov 14, 2018 · The flow cytometry assay designed to quantify peripheral blood monocyte subsets was implemented by multiple diagnosis laboratories in France. A ...
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Time- and Race-Specific Haematological Reference Intervals ... - NIH
Mar 13, 2020 · This study indicates that black individuals on average had lower total WBC, neutrophil, monocyte, eosinophil, and basophil counts than ...
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Inherited and Environmental Factors Influence Human Monocyte ...
A trans-ethnic meta-analysis study revealed that those of a European ancestry tend to have a higher monocyte count compared to African-American and Japanese ...
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Peripheral monocytosis as a predictive factor for adverse outcome in ...
The aim of the article is to study monocytosis as an outcome factor in the emergency setting. A total of 1217 patients with monocytosis were identified.
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(PDF) Can Monocytopenia Be a New Indicator in Determining ...
Aug 7, 2025 · Background: Monocytes play a central role in Covid-19 infection. Monocytopenia is especially observed in patients with severe infection.
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Monocytopenia, monocyte morphological anomalies and ...
COVID‐19 infection causes a decrease in circulating lymphocyte and monocyte populations associated with severity of disease in patients with T2D. •. Monocytes ...
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Human CD16+ monocytes promote a pro-atherosclerotic endothelial ...
May 25, 2021 · Aims: Monocytes are central for atherosclerotic vascular inflammation. The human non-classical, patrolling subtype, which expresses high ...
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Monocytes in rheumatoid arthritis: Circulating precursors ... - PubMed
They skew towards mainly intermediate monocyte subsets (CD14++ CD16+) which produce proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. Moreover, the ...
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TNF-α Inhibitors Decrease Classical CD14 hi CD16- Monocyte ...
Jan 12, 2019 · Monocytes are pivotal cells in inflammatory joint diseases. We aimed to determine the effect of TNF-α inhibitors (TNFi) on peripheral blood ...
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Tumour-associated macrophages are a distinct M2 polarised ...
Evidence is presented here supporting the view that TAM represent a unique and distinct M2-skewed myeloid population and are a potential target for anti-cancer ...
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Tumor-associated leukemia inhibitory factor and IL-6 ... - PubMed
Dec 15, 2007 · Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells. Blood. 2007 ...
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Smart Cell Therapy: an industry perspective on macrophages as ...
This review explores the potential of macrophages to orchestrate both innate and adaptive immune responses, enhancing the body's ability to combat diseases.
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Role of pyruvate kinase M2 in regulating sepsis (Review) - PMC
The occurrence of sepsis is closely associated with the hyperactivation of immune cells and cytokine storms (33). The role of PKM2 in immune cells therefore ...
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Calming the inflammatory storm in severe COVID-19 infections
A cytokine environment induces inflammatory CD14 + CD16 + monocytes, which expresses IL-6 and accelerates inflammation. SARS-CoV-2 virus causes aberrant immune ...
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Non-Malignant Granulocyte and Monocyte Disorders: An Update
Oct 10, 2025 · In contrast, GATA2 deficiency generates isolated monocytopenia, correlating with a broadened window for opportunistic pathogens. Frontline ...
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Monocyte function in the acquired immune deficiency syndrome ...
Monocytes from each of the AIDS patients with Kaposi's sarcoma and/or opportunistic infection exhibited a marked reduction in chemotaxis to all stimuli.
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Kinetics of proinflammatory monocytes in a model of ... - PubMed
Proinflammatory circulating monocytes have important roles in the pathology of multiple sclerosis (MS) and its animal model, experimental autoimmune ...Missing: plaques | Show results with:plaques
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Improving Blood Monocyte Energy Metabolism Enhances Its Ability ...
Jun 15, 2023 · This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel ...
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Roles of blood monocytes carrying TREM2 R47H mutation in ...
Dec 30, 2024 · Our study reveals that blood monocytes carrying the TREM2 R47H mutation substantially contribute to the pathogenesis of AD.
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Therapeutic depletion of monocyte-derived cells protects from long ...
Jan 15, 2016 · We show that long-lasting depletion of MDCs, after onset of EAE clinical deficits, is accompanied by decreased CNS infiltration by pathogenic T lymphocytes.
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Depletion of Peripheral Monocytes Alters Long-Term Gene ...
Sep 9, 2025 · These data shows that short-course of peri-injury depletion of peripheral monocytes may have a neuroprotective effect after TBI.
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Ly6C hi monocytes in the inflamed colon give rise to ... - PubMed
Dec 14, 2012 · We showed that CCR2 expression is essential to the recruitment of Ly6C(hi) monocytes to the inflamed gut to become the dominant mononuclear cell ...
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The microbiota-gut-brain-immune interface in the pathogenesis of ...
Gut microbiota influence brain function by way of maintenance of homeostasis in innate and adaptive immunity, limiting acute and chronic inflammation in the gut ...