TH17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity

被引：81
作者：
Harbour, Stacey N. [1 ]
DiToro, Daniel F. [1 ]
Witte, Steven J. [1 ]
Zindl, Carlene L. [1 ]
Gao, Min [2 ,3 ]
Schoeb, Trenton R. [2 ]
Jones, Gareth W. [4 ,5 ,6 ]
Jones, Simon A. [5 ,6 ]
Hatton, Robin D. [1 ]
Weaver, Casey T. [1 ]
机构：
[1] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA
[3] Univ Alabama Birmingham, Informat Inst, Birmingham, AL 35294 USA
[4] Univ Bristol, Sch Cellular & Mol Med, Bristol, Avon, England
[5] Cardiff Univ, Syst Immun Univ Res Inst, Cardiff CF14 4XN, S Glam, Wales
[6] Cardiff Univ, Sch Med, Div Infect & Immun, Cardiff CF14 4XN, S Glam, Wales
来源：
SCIENCE IMMUNOLOGY | 2020年 / 5卷 / 49期
基金：
英国惠康基金;
关键词：
CHRONIC INTESTINAL INFLAMMATION; SOLUBLE INTERLEUKIN-6 RECEPTOR; GENOME-WIDE ASSOCIATION; CD4(+) T-CELLS; REGULATED EXPRESSION; TH17; CELLS; CYTOKINE; DIFFERENTIATION; PLASTICITY; GP130;
D O I：
10.1126/sciimmunol.aaw2262
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Acting in concert with TGF-beta., interleukin-6 (IL-6) signaling induces T helper 17 (T(H)17) cell development by programming T(H)17-related genes via signal transducers and activators of transcription 3 (STAT3). A role for IL-6 signaling beyond the inductive phase of T(H)17 cell development has not been defined because IL-23 signaling downstream of T(H)17 cell induction also activates STAT3 and is thought responsible for T(H)17 cell maintenance. Here, we find that IL-6 signaling is required for both induction and maintenance of mouse T(H)17 cells; IL-6R alpha-deficient T(H)17 cells rapidly lost their T(H)17 phenotype and did not cause disease in two models of colitis. Cotransfer of wild-type T(H)17 cells with IL-6R.-deficient T(H)17 cells induced colitis but was unable to rescue phenotype loss of the latter. High IL-6 expression in the colon promoted classic, or cis, rather than transreceptor signaling that was required for maintenance of T(H)17 cells. Thus, ongoing classic IL-6 signaling underpins the T(H)17 program and is required for T(H)17 cell maintenance and function.
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页数：16
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