期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：25
页码：11495-11500
DOI：10.1073/pnas.1002099107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Dendritic cells (DCs) play a central role in determining the induction of T cell responses. IL-27 production by DCs favors induction of IL-10-producing regulatory T cells, whereas osteopontin (OPN) promotes pathogenic IL-17 T cell responses. The regulatory mechanisms in DCs that control these two cells types are not understood well. Here, we show that IFN-{gamma} induces IL-27 while inhibiting OPN expression in DCs both in vitro and in vivo and that engagement of IFN-{gamma}R expressed by DCs leads to suppression of IL-17 production while inducing IL-10 from T cells. DCs modified by IFN-{gamma} acquire IL-27-dependent regulatory function, promote IL-10-mediated T cell tolerance, and suppress autoimmune inflammation. Thus, our results identify a previously unknown pathway by which IFN-{gamma} limits IL-17-mediated autoimmune inflammation through differential regulation of OPN and IL-27 expression in DCs.
