IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection

被引:3
|
作者
Harker, James A. [1 ,2 ]
Greene, Trever T. [1 ]
Barnett, Burton E. [1 ]
Bao, Phuc [1 ]
Dolgoter, Aleksandr [1 ]
Zuniga, Elina I. [1 ]
机构
[1] Univ Calif San Diego, Dept Biol Sci, Div Mol Biol, La Jolla, CA 92161 USA
[2] Imperial Coll London, Natl Heart & Lung Inst, London, England
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
基金
英国惠康基金; 美国国家卫生研究院;
关键词
chronic viral infection; lcmv; IL-6; IL-27; T follicular helper cells; FOLLICULAR HELPER; STAT3; DIFFERENTIATION; MODULATION; EXPRESSION; BLOCKADE;
D O I
10.3389/fimmu.2023.1221562
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 IL-6 cytokine family signals through the common signal transduction molecule gp130 combined with a cytokine-specific receptor. Gp130 signaling on CD4 T cells is vital in controlling chronic infection of mice with lymphocytic choriomeningitis virus clone 13 (LCMV Cl13), but the precise role of individual members of the IL-6 cytokine family is not fully understood. Transcriptional analysis highlighted the importance of gp130 signaling in promoting key processes in CD4 T cells after LCMV Cl13 infection, particularly genes associated with T follicular helper (Tfh) cell differentiation and IL-21 production. Further, Il27r(-/-)Il6ra(-/-) mice failed to generate antibody or CD8 T-cell immunity and to control LCMV Cl13. Transcriptomics and phenotypic analyses of Il27r(-/-)Il6ra(-/-) Tfh cells revealed that IL-6R and IL-27R signaling was required to activate key pathways within CD4 T cells. IL-6 and IL-27 signaling has distinct and overlapping roles, with IL-6 regulating Tfh differentiation, IL-27 regulating CD4 T cell survival, and both redundantly promoting IL-21.
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页数:11
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