An essential role for the IL-2 receptor in Treg cell function

被引:662
作者
Chinen, Takatoshi [1 ,2 ]
Kannan, Arun K. [3 ,9 ]
Levine, Andrew G. [1 ,2 ]
Fan, Xiying [1 ,2 ]
Klein, Ulf [4 ,5 ,6 ]
Zheng, Ye [7 ]
Gasteiger, Georg [1 ,2 ,8 ]
Feng, Yongqiang [1 ,2 ]
Fontenot, Jason D. [3 ,10 ]
Rudensky, Alexander Y. [1 ,2 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA
[2] Mem Sloan Kettering Canc Ctr, Immunol Program, 1275 York Ave, New York, NY 10021 USA
[3] Biogen, Immunol Discovery, Cambridge, MA USA
[4] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA
[5] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA
[6] Columbia Univ, Dept Microbiol & Immunol, New York, NY USA
[7] Salk Inst Biol Studies, Nomis Fdn, Labs Immunobiol & Microbial Pathogenesis, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA
[8] Johannes Gutenberg Univ Mainz, Med Ctr, Inst Med Microbiol & Hyg, Mainz, Germany
[9] AbbVie, Biotechnol, N Chicago, IL 60064 USA
[10] Juno Therapeut, Exploratory Biol, Seattle, WA 98109 USA
基金
美国国家卫生研究院; 日本学术振兴会;
关键词
TRANSCRIPTION FACTOR FOXP3; IN-VIVO; SUPPRESSOR FUNCTION; CUTTING EDGE; INTERLEUKIN-2; EXPRESSION; INDUCTION; LINEAGE; STAT5; GENE;
D O I
10.1038/ni.3540
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Regulatory T cells (T-reg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by T-reg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the T-reg cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of T-reg cells. Using genetic gain-and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4(+) T cells but was important for limiting the activation of CD8(+) T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of T-reg cells separable from signaling via the T cell antigen receptor.
引用
收藏
页码:1322 / 1333
页数:12
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