Development of Monocytes, Macrophages, and Dendritic Cells

Abstract

Monocytes and macrophages are critical effectors and regulators of inflammation and the innate immune response, the immediate, pre-programmed arm of the immune system. Dendritic cells initiate and regulate the highly pathogen-specific adaptive immune responses, and are central to the development of immunologic memory and tolerance. Recent in vivo experimental approaches in the mouse have unveiled new aspects of the developmental and lineage relationships among these cell populations. Despite this, the origin and differentiation cues for many tissue macrophages, monocytes, and dendritic cell subsets in mice, and the corresponding cell populations in humans, remain to be elucidated.White blood cells or leukocytes are a diverse group of cell types that mediate the body's immune response. They circulate through the blood and lymphatic system and are recruited to sites of tissue damage and infection. Leukocyte subsets are distinguished by functional and physical characteristics. They have a common origin in hematopoietic stem cells and develop along distinct differentiation pathways in response to internal and external cues. The mononuclear phagocyte system represents a subgroup of leucocytes originally described as a population of bone marrow-derived myeloid cells that circulate in the blood as monocytes and populate tissues as macrophages in the steady state and during inflammation (1). In different tissues they can show significant heterogeneity with respect to phenotype, homeostatic turnover and function. The discovery of dendritic cells (DCs) as a distinct lineage of mononuclear phagocytes, specialized in antigen presentation to T cells and the initiation and control of immunity (2), revealed additional roles of these cells in shaping the immune response to pathogens, vaccines and tumors, as well as additional heterogeneity. Whereas a detailed map of the relationship between monocytes, DCs and their progenitors begins to emerge, other areas like the origin and renewal of tissue macrophage subsets remain less defined. (Fig. 1A) circulate in the blood, bone marrow, and spleen and do not proliferate in a steady state (3,4). Monocytes represent immune effector cells, equipped with chemokine Monocytes

Regulation of systemic and local myeloid cell subpopulations by bone marrow cell–derived granulocyte–macrophage colony‐stimulating factor in experimental inflammatory arthritis

“…What is also unknown is the relationship between the respective monocyte and tissue macrophage subpopulations in arthritic disease, as well as more generally in other inflammatory/autoimmune conditions (47). The reduction in synovial Ly-6C high macrophages following GM-CSF depletion in both the CIA and K/BxN serum-transfer models, paralleling the reduction in circulating Ly-6C high monocytes, implies that there might be a GM-CSF-dependent relationship between these respective populations in blood and tissue.…”

Cancer‐promoting tumor‐associated macrophages: New vistas and open questions

“…In a transplanted mammary carcinoma in normoxic and hypoxic areas TAMs were reported to have an M1-like and M2-like phenotype, respectively [30]. The microanatomical distributions of cells with different phenotypes and their relation to monocyte subsets [30] remain to be determined, however.…”

Diversity and plasticity of mononuclear phagocytes

“…F4/80 has been followed by a number of molecules associated with mononuclear phagocyte differentiation, subset composition and polarisation [2]. Transcriptional profiling has contributed new candidate molecules.…”

“…Mononuclear phagocytes constitute a system characterised by considerable diversity. Indeed, two major themes have emerged in recent macrophage investigations: their heterogeneity in different tissue environments and phenotypic plasticity in various physiologic and pathologic states [2][3][4][5]. Macrophages contribute to tissue homeostasis by the clearance of effete and injured host components and to defence against infection by phagocytosis and microbial killing.…”