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

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

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Innate immune recognition is critical for the induction of adaptive immune responses; however the underlying mechanisms remain incompletely understood. Here, we demonstrate that T cell-specific deletion of the IL-6 receptor a chain (IL-6Ra) results in impaired Th1 and Th17 T cell responses in vivo, and a defect in the 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-1|3 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-6Ra-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.

Original languageEnglish (US)
Article number01949
JournaleLife
Volume2014
Issue number3
DOIs
StatePublished - May 19 2014
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Nish, S. A., Schenten, D., Wunderlich, T., Pope, S. D., Gao, Y., Hoshi, N., Yu, S., Yan, X., Lee, H. K., Pasman, L., Brodsky, I., Yordy, B., Zhao, H., Bruning, J., & Medzhitov, R. (2014). T cell-intrinsic role of IL-6 signaling in primary and memory responses. eLife, 2014(3), [01949]. https://doi.org/10.7554/eLife.01949