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

被引：98

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.

引用

页数：16

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