Monocytes express various receptors, which monitor and sense environmental changes. Ykl40 is a macrophage derived factor that serves as a wellknown serum marker of. Monocyte derived macrophages mom can also acquire a kclike phenotype after inflammation. Monocytederived macrophages mom can also acquire a kclike phenotype after inflammation.
There is a substantial heterogeneity among each macrophage population, which most probably reflects the required level of specialisation within the environment of any given tissue. Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. Regulation of monocyte functional heterogeneity by mir. Macrophage heterogeneity is the main feature of the tumour microenvironment. Recent advances in our understanding of macrophage heterogeneity in response to their microenvironment raise new and exciting therapeutic possibilities to attenuate or conceivably reverse progressive renal disease in the context of fibrosis. Peritonitis remains the major obstacle for the maintenance of longterm peritoneal dialysis and dysregulated host peritoneal immune responses may compromise local antiinfectious defense, leading to treatment failure. A infarct site inflammatory cell populations expand rapidly following ami with an initial expansion of ly6c high monocytes, peaking day 35, followed by an expansion of ly6c low macrophages, peaking on day 7. Until recently, human monocytes were subdivided based on expression of the surface marker cd16. Clinical significance of monocyte heterogeneity pdf. Numerous antimacrophage antibodies were produced, with a consequent subdivision of macrophages into many subpopulations. In two recent publications, a specific contribution of certain monocyte subsets to atherogenesis was confirmed. In this context, they outline emerging concepts in monocyte heterogeneity, emergency monopoiesis, and trained immunity, and discuss new perspectives in monocyte research.
Gaps and future directions in understanding monocyte heterogeneity recent adherence to the tripartite description of monocytes based on expression of cd14 and cd16 along with standardized gating strategies has enabled investigators to more thoroughly explore the nature of monocyte differentiation and function in human disease. The existence of monocytes has been appreciated since at least the 1920s 5. Jci insight singlecell analysis of fatemapped macrophages. Mildner, guilliams, and yona discuss how the advent of new technologies such as fatemapping and singlecell analysis have revised our thinking on monocyte origin and function. While intratumoral accumulation of nanomedicines combined with immunomodulation would significantly enhance therapeutic efficacy, such potential is challenged by the compressed environment and distinct heterogeneity of the tumor. The inner region of solid tumors is found to be highpressure, hypoxic, and immunosuppressive, providing a breeding ground for tumor aggressiveness and metastasis. Monocyte and macrophage plasticity in tissue repair and regeneration. Furthermore, it is important not to overinterpret the expression of a single marker, such as cd11c, as indicative of.
Though not dogmatic, general recognition that classical monocytes arise from the bone marrow and give rise to intermediate and. The nature of monocytemacrophage heterogeneity is also difficult to assess due to the considerable plasticity of macrophages, their repertoire of receptors and extensive biosynthetic capacity. Here we outline emerging concepts in monocyte heterogeneity, emergency. The nature of monocyte macrophage heterogeneity is also difficult to assess due to the considerable plasticity of macrophages, their repertoire of receptors and extensive biosynthetic capacity. Gene expression profiling reveals the defining features of. Developmental and functional heterogeneity of monocytes. Moreover, the systemic nature of these interactions. We therefore phenotyped monocytes from peripheral blood of. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. The interaction of ccl2ccr2 and cx3cl1cx3cr1 pair mediates egress of circulating monocytes and their recruitment into the ra synovium 6, 71, 97. Monocyte differentiation and macrophage polarization.
Significant heterogeneity exists in the monocytemacrophage phenotype, which has been investigated functionally, morphologically, through cell surface markers, and more recently through genetically altered mouse models. Over the past two decades, considerable attention to monocyte. Gels were loaded with 40,000 dpmlane and evaluated by phosphorimage analysis. Yeung, 1 nikollaq vozhilla, 1 ada weinstock, 2 stephen a. Pdf monocytes and macrophages have crucial and distinct roles in tissue homeostasis and immunity. Clinical significance of monocyte heterogeneity brian k stansfield1,2,6 and david a ingram3,4,5 abstract monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Nonclassical monocytes were often referred to as proinflammatory, secondary to their mobilization in disease and secretion of important inflammatory cytokines 7,911 i. Peritoneal macrophage heterogeneity is associated with. Monocyte heterogeneity in obesity and subclinical atherosclerosis. The new tripartite view of monocyte subpopulations has shifted attention from the inflammatory. Monocyte and macrophage heterogeneity and tolllike. The role of macrophages in medulloblastoma, the most common malignant pediatric brain tumor, is unclear. Not long ago, monocyte heterogeneity, monocyte heterogeneity was established in a murine model, 18 enabling researchers to study monocyte subsets in models of atherosclerosis. Monocytes are highly plastic and heterogeneous, and change their functional phenotype in response to environmental stimulation.
Phenotype, function, and differentiation potential of. Ykl40 is a macrophagederived factor that serves as a wellknown serum marker of. Monocytes exist in at least two subsets, which are committed to divergent functions. Evidence from murine and human studies has suggested that monocytosis can be an indicator of various inflammatory diseases. But inflammation and monocytes are also involved in the pathogenesis of inflammatory diseases, including atherosclerosis. Although monocytes maintain several tissuespecific populations of immune cells in homeostasis, their contribution to populations of dendritic cells, macrophages, and osteoclasts is significantly increased in inflammation. Cardiac monocytes and macrophages after myocardial infarction. They leave the circulation by squeezing through the blood vessel wall in a specialized process known as diapedesis, to give rise to heterogeneous tissue macrophages. Monocyte and macrophage heterogeneity in giant cell arteritis and polymyalgia.
Additionally new macrophage tracers could be designed to replace 18ffluorodeoxyglucose fdg as a more cell specific tracer in petct scans. B by 6 weeks, inflammatory cell infiltration at the infarct site has returned to baseline, leaving an acellular collagen. Furthermore, it is important not to overinterpret the expression of a single marker, such as cd11c, as indicative of dc differentiation. Sep 23, 2019 although these functions have not all been investigated in terms of monocyte heterogeneity and or mirna context, the mir146relb axis might be the missing link with bmal1dependent regulation of ly6c high diurnal variations controlling their trafficking to sites of inflammation, ahrdependent regulation of ly6c high monocyte derived dc. Monocyte derived macrophages represent the key cell type of the innate immune system. Distinct monocyte populations give rise to dc 111, activated 111 and fibrogenic 18 macrophages gordon and pluddemann bmc biology 2017 15. Monocytederived macrophages represent the key cell type of the innate immune system. This may explain the heterogeneity character of monocyte subsets and their polarization into their own other subsets as per demand in the ra synovium. However, as we discuss here, recent studies have shown that. After birth, bone marrow derived blood monocytes re. Both may be useful but these cells became valid diagnostic tools only when monocyte subsets are determined. However, the subsequent identifica tion of differential expression of antigenic markers showed that monocytes in human peripheral blood are hetero geneous. The plasticity of macrophages plays a decisive role in tissue repair and regeneration.
Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Review developmental and functional heterogeneity of monocytes. The idea that monocytes derive from bone marrow precursors, circulate, and give rise to tissue macrophages was consolidated in the 1960s and has dominated much of our thinking since 6. Monocyte and macrophage dynamics in the cardiovascular. Macrophages originate from blood monocytes that leave the circulation to differentiate in different tissues. Concomitantly, immunological imprinting of either tolerance immunosuppression or trained immunity innate immune memory determines the functional fate of monocytes and monocytederived macrophages, as observed after infection or vaccination. Clinical significance of monocyte heterogeneity clinical. Monocytosis is the state of excess monocytes in the peripheral blood. Tumor cells evade immune responses by producing high levels of retinoic acid, which directs intratumoral monocytes to differentiate into immunosuppressive macrophages rather than immunostimulatory dendritic cells.
Tumorderived retinoic acid regulates intratumoral monocyte. Furthermore, parallels with pathological processes in many other organs also exist. Concomitantly, immunological imprinting of either tolerance immunosuppression or trained immunity innate immune memory determines the functional fate of monocytes and monocyte derived macrophages, as observed after infection or vaccination. By interacting with epithelial, stromal and immune cells in the lung, they maintain alveolar integrity and orchestrate responses to environmental challenges. The heterogeneity of ly6chi monocytes controls their. Singlecell analysis of fatemapped macrophages reveals heterogeneity, including stemlike properties, during atherosclerosis progression and regression jianda lin, 1 hitoo nishi, 2 jordan poles, 1 xiang niu, 4 caroline mccauley, 1 karishma rahman, 2 emily j. Monocytetomacrophage differentiation is accompanied by changes in proteoglycan synthesis. A major characteristic of the model is that macrophage development follows a linear and spatiallyrestricted.
Sources of heterogeneity in human monocyte subsets. However, macrophage polarization patterns in different tumour stages and the importance of its relationship to human epidermal growth factor receptor 2 her2 in breast cancer remains highly unclear. Cardiac monocytes and macrophages after myocardial. The most abundant one is composed by embryonicallyderived kupffer cells kc which reside in liver sinusoids and interact mainly with hsc and ec. Our findings reveal differential recruitment of macrophages with molecular. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. Clinical significance of monocyte heterogeneity pdf paperity. Blood monocytes are precursors of dendritic cells, macrophages, and osteoclasts. Classical monocytes represent the largest population of monocytes and are important scavenger cells. Request pdf monocyte and macrophage heterogeneity in the heart monocytes and macrophages are innate immune cells that reside and accumulate in the healthy and injured heart. Gordon s, taylor pr 2005 monocyte and macrophage heterogeneity. Documentation of normal function and variation in this complement of subtypes, particularly their differentiation potential to dendritic cells dc or macrophages, remains incomplete.
As an example, tcell heterogeneity is essential for an effective immune response. They play an important role in many inflammatory diseases including atherosclerosis or cancer 2. Monocyte and macrophage heterogeneity semantic scholar. Frontiers understanding the heterogeneity of resident liver. Pdf link pdf citation r andreesen, kj bross, j osterholz, f emmrich.
Mps, which they share with macrophages and conventional dendritic cells cdc guilliams et al. Frontiers understanding the heterogeneity of resident. University of groningen monocyte and macrophage heterogeneity. Download fulltext pdf download fulltext pdf download fulltext pdf clinical significance of monocyte heterogeneity article pdf available in clinical and translational medicine 41. An in vitro model to study heterogeneity of human macrophage. Monocyte and macrophage heterogeneity in the heart circulation. Blood monocyte subpopulations also express phenotypic differences that reflect heterogeneity associated with their origin, maturation and activation 18, 21, 22. Alveolar macrophages are tissueresident cells that line the inner epithelial surface of the alveoli and play a crucial role in lung development, surfactant homeostasis and immune surveillance. Pdf clinical significance of monocyte heterogeneity. In adult mice, monocytes originate in the bone marrow in a csf1r mcsfr, cd115dependent manner from a.
In the immune system, monocytes, macrophages gordon and taylor, 2005, bcells, and tcells show heterogeneity. Tsujioka h, imanishi t, ikejima h, et al impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial. Monocytes and macrophages are innate immune cells that reside and accumulate in the healthy and injured heart. Monocyte and macrophage heterogeneity in the heart. The liver is populated by different macrophage populations. Gordon and others published monocyte and macrophage heterogeneity find, read and cite all the research you need on researchgate. It has long been recognized that the bone marrow is the primary site of origin for circulating monocytes that may later become macrophages in atherosclerotic lesions. Singlecell transcriptomic profile reveals macrophage. Ccl2monocyte chemoattractant protein1 regulates inflammatory responses critical to healing myocardial infarcts.
A clear understanding of monocyte heterogeneity is lacking, but it is suggested that monocytes mature in the blood. Both in humans and in mice, monocytetomacrophage differentiation involves global transcriptome changes that are tightly controlled by various transcriptional regulators and signaling mechanisms. Feb 14, 2015 finally, in response to macrophage colony stimulating factor mcsf, intermediate monocytes are initially expanded in the peripheral blood followed by a delayed increase in nonclassical monocyte frequency 24,32,33. The ontogenic heterogeneity of tissue macrophage is fascinating, and raises the question of why it is that fetal. Using singlecell rna sequencing in a mouse model of sonic hedgehog medulloblastoma and analysis of bulk rna sequencing of human medulloblastoma, we investigated macrophage heterogeneity. Monocytes are circulating blood leukocytes that play important roles in the inflammatory response, which is essential for the innate response to pathogens. Aug 27, 2008 numerous anti macrophage antibodies were produced, with a consequent subdivision of macrophages into many subpopulations. A large number of clinical studies support concepts of cardiac monocyte and macrophage heterogeneity recently described in mice. Thus, studying macrophage biology is essential for increasing our knowledge on the pathophysiology of many diseases and to allow development of novel therapies.
Sources of heterogeneity in human monocyte subsets laura j. For example, macrophage populations after ir have a temporally shifted immune response, with macrophage populations at the infarct site peaking 4 days earlier than in the permanent ligation model and having almost completely resolved by 7 days. Breast cancer is one of the most lifethreatening cancers. Jci macrophage diversity in renal injury and repair. The cells and their subsets pursue distinct functions in steadystate and disease, and their tenure may range between hours and months. Additionally, since these macrophage populations are present in both.
Read monoclonal antibodies specific for porcine monocytesmacrophages. Consequences for monocytederived immune cells sarasprangers, 1 vries, 2 andvincenteverts 1 department of oral cell biology and functional anatomy, academic centre for dentistry amsterdam acta. Monocytes and macrophages are innate immune cells that reside and. Differentiation and heterogeneity in the mononuclear. Finally, in response to macrophage colony stimulating factor mcsf, intermediate monocytes are initially expanded in the peripheral blood followed by a delayed increase in nonclassical monocyte frequency 24,32,33.
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