T cell-intrinsic role of IL-6 signaling in primary and memory responses
- Yale University School of Medicine, United States
- Max Planck Institute for Neurological Research Cologne, Germany
- Yale School of Public Health, United States
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 α chain (IL-6Rα) 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-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.
Article and author information
Author details
Reviewing Editor
- Tadatsugu Taniguchi, University of Tokyo, Japan
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2011-08006) of the Yale University.
Version history
- Received: November 25, 2013
- Accepted: May 16, 2014
- Accepted Manuscript published: May 19, 2014 (version 1)
- Version of Record published: June 10, 2014 (version 2)
Copyright
© 2014, Nish et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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T cell-intrinsic role of IL-6 signaling in primary and memory responses
eLife 3:e01949.
https://doi.org/10.7554/eLife.01949
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