Th17 Cells Express Interleukin-10 Receptor and Are Controlled by Foxp3- and Foxp3+ Regulatory CD4+ T Cells in an Interleukin-10-Dependent Manner

被引:510
作者
Huber, Samuel [1 ,3 ]
Gagliani, Nicola [4 ,5 ]
Esplugues, Enric [1 ,6 ,7 ]
O'Connor, William, Jr. [1 ]
Huber, Francis J. [1 ]
Chaudhry, Ashutosh [8 ]
Kamanaka, Masahito [1 ]
Kobayashi, Yasushi [1 ]
Booth, Carmen J. [2 ]
Rudensky, Alexander Y. [8 ]
Roncarolo, Maria Grazia [5 ,9 ]
Battaglia, Manuela [4 ]
Flavell, Richard A. [1 ,10 ]
机构
[1] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Comparat Med Sect, New Haven, CT 06520 USA
[3] Univ Klinikum Hamburg Eppendorf, Med Klin 1, D-20246 Hamburg, Germany
[4] San Raffaele Diabet Res Inst HSR DRI, I-20132 Milan, Italy
[5] Univ Vita Salute San Raffaele, I-20132 Milan, Italy
[6] German Rheumatism Res Ctr DRFZ, D-10117 Berlin, Germany
[7] Charite, Cluster Excellence NeuroCure, D-10117 Berlin, Germany
[8] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA
[9] Dept Regenerat Med Stem Cells & Gene Therapy HSR, I-20132 Milan, Italy
[10] Howard Hughes Med Inst, Chevy Chase, MD USA
关键词
INFLAMMATORY-BOWEL-DISEASE; INTESTINAL INFLAMMATION; CRUCIAL ROLE; TGF-BETA; MICE; IL-10; RESPONSES; COLITIS; T(H)17; DIFFERENTIATION;
D O I
10.1016/j.immuni.2011.01.020
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T helper 17 (Th17) cells are important for host defense against extracellular microorganisms. However, they are also implicated in autoimmune and chronic inflammatory diseases, and as such need to be tightly regulated. The mechanisms that directly control committed pathogenic Th17 cells in vivo remain unclear. We showed here that IL-17A-producing CD4(+) T cells expressed interleukin-10 receptor alpha (IL-10R alpha) in vivo. Importantly, T cell-specific blockade of IL-10 signaling led to a selective increase of IL-17A(+)IFN-gamma(-) (Th17) and IL-17A(+)IFN-gamma(+) (Th17+Th1) CD4(+) T cells during intestinal inflammation in the small intestine. CD4(+)Foxp3(-) IL-10-producing (Tr1) cells and CD4(+)Foxp3(+) regulatory (Treg) cells were able to control Th17 and Th17+Th1 cells in an IL-10-dependent manner in vivo. Lastly, IL-10 treatment of mice with established colitis decreased Th17 and Th17+Th1 cell frequencies via direct signaling in T cells. Thus, IL-10 signaling directly suppresses Th17 and Th17+Th1 cells.
引用
收藏
页码:554 / 565
页数:12
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