C5a receptor-deficient dendritic cells promote induction of Treg and Th17 cells.
C5a receptor-deficient dendritic cells promote induction of Treg and Th17 cells.
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DOI：
10.1002/eji.200939333
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发表时间：
2010-03
影响因子：
5.4
通讯作者：
Koehl, Joerg
中科院分区：
文献类型：
--
作者：
Weaver, Donald J., Jr.;Reis, Edimara S.;Pandey, Manoj K.;Koehl, Gabriele;Harris, Nathaniel;Gerard, Craig;Koehl, Joerg
C5 a是一种促炎介质，最近已被证明可以调节适应性免疫反应。在这里，我们证明了树突状细胞（DC）中的C5 a受体（C5 aR）信号影响调节性T细胞（Treg）和Th 17细胞的发育。脾源性DC中C5 aR的遗传消融或药理学靶向导致TGF-β的产生增加，导致Foxp 3 + Treg在与来自DO11.10/RAG 2-/-小鼠的CD 4 + T细胞共孵育后12小时内重新分化。用卵清蛋白和TLR 2配体Pam 3CSK 4刺激C5 aR-/- DC增加TGF-β产生并诱导高水平的IL-6和IL-23，但仅诱导少量的IL-12，导致产生IL-17 A和IL-21的Th细胞分化。在将CD 4 + Th细胞过继转移到用OVA和Pam 3CSK 4免疫的C5 aR-/-小鼠中后，体内也发现Th 17分化。C5 aR-/- DC的细胞因子产生的改变与低稳态MHCII类表达和响应于TLR 2上调CD 86和CD 40的能力受损相关。我们的数据表明C5 aR通过调节DC功能在Treg和Th 17细胞分化中起关键作用。
C5a is a proinflammatory mediator that has recently been shown to regulate adaptive immune responses. Here we demonstrate that C5a receptor (C5aR) signaling in dendritic cells (DC) affects the development of regulatory T cell (Treg) and Th17 cells. Genetic ablation or pharmacological targeting of the C5aR in spleen-derived DC results in increased production of TGF-β leading to de novo differentiation of Foxp3+ Treg within 12h after co-incubation with CD4+ T cells from DO11.10/RAG2-/- mice. Stimulation of C5aR-/- DC with ovalbumin and TLR2 ligand Pam3CSK4 increased TGF-β production and induced high levels of IL-6 and IL-23 but only minor amounts of IL-12 leading to differentiation of Th cells producing IL-17A and IL-21. Th17 differentiation was also found in vivo after adoptive transfer of CD4+ Th cell into C5aR-/- mice immunized with OVA and Pam3CSK4. The altered cytokine production of C5aR-/- DC was associated with low steady state MHC class II expression and an impaired ability to upregulate CD86 and CD40 in response to TLR2. Our data suggest critical roles for C5aR in Treg and Th17 cell differentiation through regulation of DC function.
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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