In Vivo Analysis of Dendritic Cell Development and Homeostasis

Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
Science (Impact Factor: 33.61). 04/2009; 324(5925):392-7. DOI: 10.1126/science.1170540
Source: PubMed


Dendritic cells (DCs) in lymphoid tissue arise from precursors that also produce monocytes and plasmacytoid DCs (pDCs). Where DC and monocyte lineage commitment occurs and the nature of the DC precursor that migrates from the bone marrow to peripheral lymphoid organs are unknown. We show that DC development progresses from the macrophage and DC precursor to common DC precursors that give rise to pDCs and classical spleen DCs (cDCs), but not monocytes, and finally to committed precursors of cDCs (pre-cDCs). Pre-cDCs enter lymph nodes through and migrate along high endothelial venules and later disperse and integrate into the DC network. Further cDC development involves cell division, which is controlled in part by regulatory T cells and fms-like tyrosine kinase receptor-3.

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Available from: Pierre Guermonprez, Apr 22, 2014
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    • "+ ) can only generate cDCs [165]. Thus, it is possible that GM-CSF merely acts as a growth factor for certain DC precursors in vivo, whose increased turnover leads to the observed increase in DC numbers after GM-CSF treatment. "
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    ABSTRACT: GM-CSF was originally identified as a colony stimulating factor (CSF) because of its ability to induce granulocyte and macrophage populations from precursor cells. Multiple studies have demonstrated that GM-CSF is also an immune-modulatory cytokine, capable of affecting not only the phenotype of myeloid lineage cells, but also T-cell activation through various myeloid intermediaries. This property has been implicated in the sustenance of several autoimmune diseases like arthritis and multiple sclerosis. In contrast, several studies using animal models have shown that GM-CSF is also capable of suppressing many autoimmune diseases such as Crohn's disease, Type-1 diabetes, Myasthenia gravis and experimental autoimmune thyroiditis. Knockout mouse studies have suggested that the role of GM-CSF in maintaining granulocyte and macrophage populations in the physiological steady state is largely redundant. Instead, its immune-modulatory role plays a significant role in the development or resolution of autoimmune diseases. This is mediated either through the differentiation of precursor cells into specialized non-steady state granulocytes, macrophages and dendritic cells, or through the modulation of the phenotype of mature myeloid cells. Thus, outside of myelopoiesis, GM-CSF has a profound role in regulating the immune response and maintaining immunological tolerance. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Cytokine 06/2015; 75(2). DOI:10.1016/j.cyto.2015.05.030 · 2.66 Impact Factor
    • "In mice, DCs and monocytes arise from a macrophage/dendritic progenitor (MDP; Fogg et al., 2006), which produces monocytes, and a common dendritic progenitor (CDP) that is restricted to the DC fate (Shortman and Naik, 2007; Liu et al., 2009; Geissmann et al., 2010; Merad et al., 2013). The CDP produces pre–plasmacytoid DCs (pDCs) and pre– conventional DCs (cDCs), the latter of which leaves the BM and circulates in the blood before entering tissues and developing into the different DCs subsets (Naik et al., 2006, 2007; Onai et al., 2007b, 2013; Ginhoux et al., 2009; Liu et al., 2009; Onai et al., 2013). "
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    ABSTRACT: Two subsets of conventional dendritic cells (cDCs) with distinct cell surface markers and functions exist in mouse and human. The two subsets of cDCs are specialized antigen-presenting cells that initiate T cell immunity and tolerance. In the mouse, a migratory cDC precursor (pre-CDC) originates from defined progenitors in the bone marrow (BM). Small numbers of short-lived pre-CDCs travel through the blood and replace cDCs in the peripheral organs, maintaining homeostasis of the highly dynamic cDC pool. However, the identity and distribution of the immediate precursor to human cDCs has not been defined. Using a tissue culture system that supports the development of human DCs, we identify a migratory precursor (hpre-CDC) that exists in human cord blood, BM, blood, and peripheral lymphoid organs. hpre-CDCs differ from premonocytes that are restricted to the BM. In contrast to earlier progenitors with greater developmental potential, the hpre-CDC is restricted to producing CD1c(+) and CD141(+) Clec9a(+) cDCs. Studies in human volunteers demonstrate that hpre-CDCs are a dynamic population that increases in response to levels of circulating Flt3L. © 2015 Breton et al.
    Journal of Experimental Medicine 02/2015; 212(3). DOI:10.1084/jem.20141441 · 12.52 Impact Factor
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    • "In mice, splenic DCs are entirely replaced by circulating progenitors within 2 weeks (121). One would therefore expect the “adjuvant” effect of commensals on myeloid function to be transient and reversible. "
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    ABSTRACT: Granulocytes, monocytes, macrophages, and dendritic cells (DCs) represent a subgroup of leukocytes, collectively called myeloid cells. During the embryonic development of mammalians, myelopoiesis occurs in a stepwise fashion that begins in the yolk sac and ends up in the bone marrow (BM). During this process, these early monocyte progenitors colonize various organs such as the brain, liver, skin, and lungs and differentiate into resident macrophages that will self-maintain throughout life. DCs are constantly replenished from BM precursors but can also arise from monocytes in inflammatory conditions. In this review, we summarize the different types of myeloid cells and discuss new insights into their early origin and development in mice and humans from fetal to adult life. We specifically focus on the function of monocytes, macrophages, and DCs at these different developmental stages and on the intrinsic and environmental influences that may drive these adaptations.
    Frontiers in Immunology 09/2014; 5:423. DOI:10.3389/fimmu.2014.00423
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