Monocyte-Derived Dendritic Cells Promote Th Polarization, whereas Conventional Dendritic Cells Promote Th Proliferation

Monocyte-Derived Dendritic Cells Promote Th Polarization, whereas Conventional Dendritic Cells Promote Th Proliferation
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DOI:
10.4049/jimmunol.1501202
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发表时间:
2016-01-15
影响因子:
4.4
通讯作者:
Zhan, Yifan
Zhan, Yifan
中科院分区:
医学2区
文献类型:
--
作者:
Chow, Kevin V.;Lew, Andrew M.;Zhan, Yifan

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单核细胞来源的树突状细胞(moDCs)在感染和炎症时数量急剧增加;因此,我们发现这也发生在同种异体反应期间。尽管它们很突出,但新兴的moDC和常驻的常规DC(cDC)如何分工作为APC仍然不确定。因此,我们比较了鼠moDC与cDC的直接和间接呈递。我们发现,尽管具有等同的MHC II类表达和体外存活,但moDCs通过直接和间接Ag呈递诱导CD 4(+)T细胞增殖的效率比cDCs低20倍。尽管如此,moDC在诱导Th 1和Th 17分化方面更有效(例如,8-在T细胞共培养物中,cDC诱导10倍更高的IFN-γ和2倍更高的IL-17 A),而cDC诱导10倍更高的IL-2产生。有趣的是,moDC有效地降低了cDC在体外和体内刺激T细胞增殖的能力,部分是通过NO的产生。我们推测moDC和cDC之间的这种分工对它们各自在免疫应答中的作用有影响。
Monocyte-derived dendritic cells (moDCs) dramatically increase in numbers upon infection and inflammation; accordingly, we found that this also occurs during allogeneic responses. Despite their prominence, how emergent moDCs and resident conventional DCs (cDCs) divide their labor as APCs remain undefined. Hence, we compared both direct and indirect presentation by murine moDCs versus cDCs. We found that, despite having equivalent MHC class II expression and in vitro survival, moDCs were 20-fold less efficient than cDCs at inducing CD4(+) T cell proliferation through both direct and indirect Ag presentation. Despite this, moDCs were more potent at inducing Th1 and Th17 differentiation (e.g., 8-fold higher IFN-gamma and 2-fold higher IL-17A in T cell cocultures), whereas cDCs induced 10-fold higher IL-2 production. Intriguingly, moDCs potently reduced the ability of cDCs to stimulate T cell proliferation in vitro and in vivo, partially through NO production. We surmise that such division of labor between moDCs and cDCs has implications for their respective roles in the immune response.