In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORγt+ T cells

被引:443
作者
Lochner, Matthias [1 ]
Peduto, Lucie [1 ]
Cherrier, Marie [1 ]
Sawa, Shinichiro [1 ]
Langa, Francina [2 ]
Varona, Rosa [5 ]
Riethmacher, Dieter [6 ]
Si-Tahar, Mustapha [3 ]
Di Santo, James P. [4 ]
Eberl, Gerard [1 ]
机构
[1] Inst Pasteur, Lab Lymphoid Tissue Dev, CNRS, URA 1961, F-75724 Paris, France
[2] Inst Pasteur, Ctr Ingn Genet Murine, F-75724 Paris, France
[3] Inst Pasteur, Unite Def Innee & Inflammat, INSERM, U874, F-75724 Paris, France
[4] Inst Pasteur, Unite Cytokines & Dev Lymphoide, INSERM, U668, F-75724 Paris, France
[5] CSIC, Dept Immunol & Oncol, Ctr Nacl Biotecnol, E-28049 Madrid, Spain
[6] Univ Southampton, Southampton Gen Hosp, Div Human Genet, Southampton SO16 6YD, Hants, England
关键词
D O I
10.1084/jem.20080034
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The nuclear hormone receptor retinoic acid receptor-related orphan receptor gamma t (ROR gamma t) is required for the generation of T helper 17 cells expressing the proinflammatory cytokine interleukin (IL)-17. In vivo, however, less than half of ROR gamma t(+) T cells express IL-17. We report here that ROR gamma t(+) T alpha beta cells include Foxp3(+) cells that coexist with IL-17-producing ROR gamma t(+) T alpha beta cells in all tissues examined. The Foxp3(+) ROR gamma t(+) T alpha beta express IL-10 and CCL20, and function as regulatory T cells. Furthermore, the ratio of Foxp3(+) to IL-17-producing ROR gamma t(+) T alpha beta cells remains remarkably constant in mice enduring infection and inflammation. This equilibrium is tuned in favor of IL-10 production by Foxp3 and CCL20, and in favor of IL-17 production by IL-6 and IL-23. In the lung and skin, the largest population of ROR gamma t(+) T cells express the gamma delta T cell receptor and produce the highest levels of IL-17 independently of IL-6. Thus, potentially antagonistic proinflammatory IL-17-producing and regulatory Foxp3(+) ROR gamma t(+) T cells coexist and are tightly controlled, suggesting that a perturbed equilibrium in ROR gamma t(+) T cells might lead to decreased immunoreactivity or, in contrast, to pathological inflammation.
引用
收藏
页码:1381 / 1393
页数:13
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