Monocytes give rise to mucosal, but not splenic, conventional dendritic cells

Varol, Chen; Landsman, Limor; Fogg, Darin K.; Greenshtein, Liat; Gildor, Boaz; Margalit, Raanan; Kalchenko, Vyacheslav; Geissmann, Frédéric; Jung, Steffen

doi:10.1084/jem.20061011

Cited by 551 publications

(585 citation statements)

References 57 publications

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“…The macrophage and DC precursor (MDP) for lymphoid tissue conventional DCs (cDCs), pDCs and monocytes is characterized as a cell expressing Lin À c-kit hi CD115 1 CX 3 CR1 1 Flt3 1 [8,26]. Another distinct progenitor is called the common DC precursor (CDP) (Lin À c-kit low CD115 1 Flt3 1 ) and is restricted to produce cDCs and pDCs, but not monocytes [27,28].…”

Section: Discussionmentioning

confidence: 99%

“…Blood monocytes can be subdivided into at least two subsets based on their Ly6C expression: classical and The nonclassical monocytes, which are Ly6C low , patrol the endothelium of the blood vessels and are required for rapid tissue invasion at the site of an infection [7]. Ly6C low monocytes are considered CD11c À , but some studies have reported the expression of CD11c on these cells [6,8]. Both types of monocytes are F4/80 1 and CD86 À [6].…”

Section: Introductionmentioning

confidence: 99%

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Abnormalities of dendritic cell precursors in the pancreas of the NOD mouse model of diabetes

et al. 2011

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The non-obese diabetic (NOD) mouse is a widely used animal model for the study of human diabetes. Before the start of lymphocytic insulitis, DC accumulation around islets of Langerhans is a hallmark for autoimmune diabetes development in this model. Previous experiments indicated that an inflammatory influx of these DCs in the pancreas is less plausible. Here, we investigated whether the pancreas contains DC precursors and whether these precursors contribute to DC accumulation in the NOD pancreas. Fetal pancreases of NOD and control mice were isolated followed by FACS using ER-MP58, Ly6G, CD11b and Ly6C. Sorted fetal pancreatic ER-MP58 1 cells were cultured with GM-CSF and tested for DC markers and antigen processing. CFSE labeling and Ki-67 staining were used to determine cell proliferation in cultures and tissues. Ly6C hi and Ly6C low precursors were present in fetal pancreases of NOD and control mice. These precursors developed into CD11c 1 MHCII 1 CD86 1 DCs capable of processing DQ-OVA. ER-MP58 1 cells in the embryonic and pre-diabetic NOD pancreas had a higher proliferation capacity. Our observations support a novel concept that pre-diabetic DC accumulation in the NOD pancreas is due to aberrant enhanced proliferation of local precursors, rather than to aberrant ''inflammatory infiltration'' from the circulation. IntroductionThe non-obese diabetic (NOD) mouse is used as a spontaneous model to study the development of type 1 diabetes [1]. Lymphocytes accumulate around and in the islets of Langerhans in NOD mice from around 6 weeks of age onwards, which results in the destruction of b-cells followed by a decrease in insulin production leading to diabetes. Prior to T-and B-cell accumulation the number of DCs increases in the pancreas and concentrates around the islets (from the age of 5 weeks onwards) [2,3]. DCs are potent APCs capable of stimulating both naïve and memory T cells [4]. The observation that DCs are the first immune cells to increase in number in the NOD pancreas points to a crucial role for DCs in the initiation of the islet autoimmune reaction. Such a role was recently proven by the demonstration that a temporal depletion of DCs totally abrogated the development of insulitis and diabetes in the NOD mouse model [5].Early studies have shown that BM precursors give rise to monocytes in blood, which circulate for a few days before they migrate into tissue where they develop into different types of DCs and macrophages. Blood monocytes can be subdivided into at least two subsets based on their Ly6C expression: classical and The nonclassical monocytes, which are Ly6C low , patrol the endothelium of the blood vessels and are required for rapid tissue invasion at the site of an infection [7]. Ly6C low monocytes are considered CD11c À , but some studies have reported the expression of CD11c on these cells [6,8]. Both types of monocytes are F4/80 1 and CD86 À [6].Data are accumulating on the presence of local tissue precursors for DCs and macrophages and the contribution of these precursors to DC and ma...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Abnormalities of dendritic cell precursors in the pancreas of the NOD mouse model of diabetes

et al. 2011

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“…Is this parasite even able to act on cells in the bone marrow? Varol et al (2007) suggested that the old scheme of myeloid differentiation as a 'one way' intermediate from the bone marrow to the periphery has to be revised, as blood monocytes can efficiently home back to the bone marrow. Another group (Becker et al, 2005) found that CD8 þ memory T cells can also reside in the BM and thus can respond faster to antigens than cells residing in other tissues.…”

Section: Discussionmentioning

confidence: 99%

In vitroinduction of lymph node cell proliferation by mouse bone marrow dendritic cells following stimulation with differentEchinococcus multilocularisantigens

et al. 2011

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The immune response of mice experimentally infected with Echinococcus multilocularis metacestodes becomes impaired so as to allow parasite survival and proliferation. Our study tackled the question on how different classes of E. multilocularis antigens (crude vesicular fluid (VF); purified proteinic rec-14-3-3; purified carbohydrate Em2(G11)) are involved in the maturation process of bone-marrow-derived dendritic cells (BMDCs) and subsequent exposure to lymph node (LN) cells. In our experiments, we used BMDCs cultivated from either naïve (control) or alveolar echinococcosis (AE)-infected C57BL/6 mice. We then tested surface markers (CD80, CD86, MHC class II) and cytokine expression levels (interleukin (IL)-10, IL-12p40 and tumour necrosis factor (TNF)-a) of non-stimulated BMDCs versus BMDCs stimulated with different Em-antigens or lipopolysaccharide (LPS). While LPS and rec-14-3-3-antigen were able to induce CD80, CD86 and (to a lower extent) MHC class II surface expression, Em2(G11) and, strikingly, also VF-antigen failed to do so. Similarly, LPS and rec-14-3-3 yielded elevated IL-12, TNF-a and IL-10 expression levels, while Em2(G11) and VF-antigen didn't. When naïve BMDCs were loaded with VF-antigen, they induced a strong non-specific proliferation of uncommitted LN cells. For both, BMDCs or LN cells, isolated from AE-infected mice, proliferation was abrogated. The most striking difference, revealed by comparing naïve with AE-BMDCs, was the complete inability of LPS-stimulated AE-BMDCs to activate lymphocytes from any LN cell group. Overall, the presenting activity of BMDCs from AE-infected mice seemed to trigger unresponsiveness in T cells, especially in the case of VF-antigen stimulation, thus contributing to the suppression of clonal expansion during the chronic phase of AE infection.

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“…Recent experiments have elegantly shed light on how lung DC subsets develop. Using adoptive transfer studies of monocytes in mice depleted of cDC, as well as using a genetic lineage tracing system employing lysozyme (Lys)MCre Â Stop/floxGFP as the reporter, it was shown that a large percentage of lung cDC do not derive from the Flt3 1 pre-cDC that seed the lymph nodes and spleen, but derive from circulating monocytes [12,19,20]. Contrasting these reports, two recent studies identified pre-cDC as the major contributing source for CD11b À CD103 1 lung cDC.…”

Section: Origin and Turnover Of Lung DC Subsetsmentioning

confidence: 99%

Origin and functional specializations of DC subsets in the lung

2010

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Lung DC bridge innate and adaptive immunity, and depending on the context, induce Th1, Th2 or Th17 response, to optimally clear infections. Conversely, lung DC can also prevent overt and harmful immune responses to harmless inhaled antigens via induction of Treg cells or via induction of neutralizing mucosal IgA antibodies. Here, we propose that these functions are not the result of a single population of DC, and instead, subsets of DC perform specialized functions.

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Monocytes give rise to mucosal, but not splenic, conventional dendritic cells

Cited by 551 publications

References 57 publications

Abnormalities of dendritic cell precursors in the pancreas of the NOD mouse model of diabetes

Abnormalities of dendritic cell precursors in the pancreas of the NOD mouse model of diabetes

In vitroinduction of lymph node cell proliferation by mouse bone marrow dendritic cells following stimulation with differentEchinococcus multilocularisantigens

Origin and functional specializations of DC subsets in the lung

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