GM-CSF-induced CD11c+CD8a-025EFdendritic cells facilitate Foxp3+and IL-10+regulatory T cell expansion resulting in suppression of autoimmune thyroiditis
GM-CSF-induced CD11c+CD8a-025EFdendritic cells facilitate Foxp3+and IL-10+regulatory T cell expansion resulting in suppression of autoimmune thyroiditis
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DOI：
10.1093/intimm/dxn147
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发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Prabhakar, Bellur S.
中科院分区：
文献类型：
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作者：
Ganesh, Balaji B.;Cheatem, Donald M.;Prabhakar, Bellur S.
GM-CSF在树突状细胞（dc）的分化中起重要作用。我们的研究表明，在小鼠模型中，GM-CSF治疗可以诱导半成熟的dc和CD4+CD25+调节性T细胞（Tregs），并抑制正在进行的自身免疫。在这项研究中，我们检测了GM-CSF在体内对dc的CD8a+和CD8a-亚群发挥耐受性功能的潜力的差异。我们发现GM-CSF通过抑制活化标记物MHC II和CD80的表面表达以及炎症细胞因子如IL-12和IL-1 β的产生，在体内调节CD8a-而不是CD8a+ dc。与gm - csf暴露的CD8a+ dc和对照CD8a+和CD8a- dc呈递抗原相比，gm - csf暴露的CD8a- dc将自身抗原[小鼠甲状腺球蛋白（mTg）]呈递至mTg诱导的小鼠T细胞诱导表达叉头盒P3 （FoxP3）的T细胞频率显著增加。加入IL-12后，GM-CD8a- dc的这种耐受性被消除。gm - csf暴露的CD8a- dc也能诱导mtg引物小鼠的T细胞分泌大量IL-10。重要的是，将CD8a- dc从GM-CSF处理的SCID小鼠（而不是未经处理的小鼠）过继转移到野生型CBA/J小鼠中，可以防止mTg免疫后受体动物发生实验性自身免疫性甲状腺炎（EAT）。总的来说，我们的研究结果表明GM-CSF使CD8a- dc产生耐受性，这些dc诱导Foxp3+和IL-10+ Tregs。
GM-CSF plays an essential role in the differentiation of dendritic cells (DCs). Our studies have shown that GM-CSF treatment can induce semi-mature DCs and CD4+CD25+ regulatory T cells (Tregs) and suppress ongoing autoimmunity in mouse models. In this study, we examined the differences in the potential of GM-CSF to exert tolerogenic function on CD8a+ and CD8a- sub-populations of DCs in vivo. We show that GM-CSF modulates CD8a-, but not CD8a+ DCs in vivo, by inhibiting the surface expression of activation markers MHC II and CD80 and production of inflammatory cytokines such as IL-12 and IL-1 beta. Self-antigen [mouse thyroglobulin (mTg)] presentation by GM-CSF-exposed CD8a- DCs to T cells from mTg-primed mice induced a profound increase in the frequency of forkhead box P3 (FoxP3)-expressing T cells compared with antigen presentation by GM-CSF-exposed CD8a+ DCs and control CD8a+ and CD8a- DCs. This tolerogenic property of GM-CD8a- DCs was abrogated when IL-12 was added. GM-CSF-exposed CD8a- DCs could also induce secretion of significantly higher amounts of IL-10 by T cells from mTg-primed mice. Importantly, adoptive transfer of CD8a- DCs from GM-CSF-treated SCID mice, but not untreated mice, into wild-type CBA/J mice prevented the development of experimental autoimmune thyroiditis (EAT) in the recipient animals upon immunization with mTg. Collectively, our results show that GM-CSF renders CD8a- DCs tolerogenic, and these DCs induce Foxp3+ and IL-10+ Tregs.