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

  1. Simone A Nish
  2. Dominik Schenten
  3. Thomas Wunderlich
  4. Scott D Pope
  5. Yan Gao
  6. Namiko Hoshi
  7. Shuang Yu
  8. Xiting Yan
  9. Heung Kyu Lee
  10. Lesley Pasman
  11. Igor Brodsky
  12. Brian Yordy
  13. Hongyu Zhao
  14. Jens Brüning
  15. Ruslan Medzhitov  Is a corresponding author
  1. Yale University School of Medicine, United States
  2. Max Planck Institute for Neurological Research Cologne, Germany
  3. 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

  1. Simone A Nish

    Yale University School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  2. Dominik Schenten

    Yale University School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  3. Thomas Wunderlich

    Max Planck Institute for Neurological Research Cologne, Cologne, Germany
    Competing interests
    No competing interests declared.
  4. Scott D Pope

    Yale University School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  5. Yan Gao

    Yale University School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  6. Namiko Hoshi

    Yale University School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  7. Shuang Yu

    Yale University School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  8. Xiting Yan

    Yale School of Public Health, New Haven, United States
    Competing interests
    No competing interests declared.
  9. Heung Kyu Lee

    Yale University School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  10. Lesley Pasman

    Yale University School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  11. Igor Brodsky

    Yale University School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  12. Brian Yordy

    Yale University School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  13. Hongyu Zhao

    Yale School of Public Health, New Haven, United States
    Competing interests
    No competing interests declared.
  14. Jens Brüning

    Max Planck Institute for Neurological Research Cologne, Cologne, Germany
    Competing interests
    No competing interests declared.
  15. Ruslan Medzhitov

    Yale University School of Medicine, New Haven, United States
    For correspondence
    ruslan.medzhitov@yale.edu
    Competing interests
    Ruslan Medzhitov, Reviewing editor, eLife.

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.

Reviewing Editor

  1. Tadatsugu Taniguchi, University of Tokyo, Japan

Publication history

  1. Received: November 25, 2013
  2. Accepted: May 16, 2014
  3. Accepted Manuscript published: May 19, 2014 (version 1)
  4. 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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  1. Simone A Nish
  2. Dominik Schenten
  3. Thomas Wunderlich
  4. Scott D Pope
  5. Yan Gao
  6. Namiko Hoshi
  7. Shuang Yu
  8. Xiting Yan
  9. Heung Kyu Lee
  10. Lesley Pasman
  11. Igor Brodsky
  12. Brian Yordy
  13. Hongyu Zhao
  14. Jens Brüning
  15. Ruslan Medzhitov
(2014)
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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