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白细胞介素-6信号在初始和记忆反应中的T细胞内在作用。

T cell-intrinsic role of IL-6 signaling in primary and memory responses.

作者信息

Nish Simone A, Schenten Dominik, Wunderlich F Thomas, Pope Scott D, Gao Yan, Hoshi Namiko, Yu Shuang, Yan Xiting, Lee Heung Kyu, Pasman Lesley, Brodsky Igor, Yordy Brian, Zhao Hongyu, Brüning Jens, Medzhitov Ruslan

机构信息

Department of Immunobiology, Yale University School of Medicine, New Haven, United States.

Max Planck Institute for Neurological Research, Cologne, Germany.

出版信息

Elife. 2014 May 19;3:e01949. doi: 10.7554/eLife.01949.

DOI:10.7554/eLife.01949
PMID:24842874
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4046568/
Abstract

Innate immune recognition is critical for the induction of adaptive immune responses; however the underlying mechanisms remain incompletely understood. In this study, we demonstrate that T cell-specific deletion of the IL-6 receptor α chain (IL-6Rα) results in impaired Th1 and Th17 T cell responses in vivo, and a defect in Tfh function. Depletion of Tregs in these mice rescued the Th1 but not the Th17 response. Our data suggest that IL-6 signaling in effector T cells is required to overcome Treg-mediated suppression in vivo. We show that IL-6 cooperates with IL-1β to block the suppressive effect of Tregs on CD4(+) T cells, at least in part by controlling their responsiveness to IL-2. In addition, although IL-6Rα-deficient T cells mount normal primary Th1 responses in the absence of Tregs, they fail to mature into functional memory cells, demonstrating a key role for IL-6 in CD4(+) T cell memory formation.DOI: http://dx.doi.org/10.7554/eLife.01949.001.

摘要

天然免疫识别对于适应性免疫应答的诱导至关重要；然而其潜在机制仍未完全阐明。在本研究中，我们证明T细胞特异性缺失白细胞介素-6受体α链（IL-6Rα）会导致体内Th1和Th17 T细胞应答受损，以及滤泡辅助性T细胞（Tfh）功能缺陷。在这些小鼠中去除调节性T细胞（Tregs）可挽救Th1应答，但不能挽救Th17应答。我们的数据表明效应T细胞中的IL-6信号传导是克服体内Treg介导的抑制作用所必需的。我们发现IL-6与IL-1β协同作用，至少部分地通过控制Tregs对IL-2的反应性，来阻断Tregs对CD4(+) T细胞的抑制作用。此外，尽管在没有Tregs的情况下，缺乏IL-6Rα的T细胞可产生正常的初始Th1应答，但它们无法成熟为功能性记忆细胞，这表明IL-6在CD4(+) T细胞记忆形成中起关键作用。DOI: http://dx.doi.org/10.7554/eLife.01949.001

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