1. Immunology and Inflammation
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The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation

  1. Agnieszka Martyna Kabat
  2. Oliver James Harrison
  3. Thomas Riffelmacher
  4. Amin E Moghaddam
  5. Claire F Pearson
  6. Adam Laing
  7. Lucie Abeler-Dörner
  8. Simon P Forman
  9. Richard K Grencis
  10. Quentin Sattentau
  11. Anna Katharina Simon
  12. Johanna Pott
  13. Kevin J Maloy  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. King's College London, United Kingdom
  3. The University of Manchester, United Kingdom
Research Article
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Cite this article as: eLife 2016;5:e12444 doi: 10.7554/eLife.12444

Abstract

A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD), however it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4+ T cell responses in the intestine. Selective deletion of Atg16l1 in T cells in mice resulted in spontaneous intestinal inflammation that was characterised by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3+ Treg cells. Specific ablation of Atg16l1 in Foxp3+ Treg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal TH2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal TH cell responses by autophagy, with important implications for understanding and treatment of chronic inflammatory disorders.

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Author details

  1. Agnieszka Martyna Kabat

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  2. Oliver James Harrison

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  3. Thomas Riffelmacher

    MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  4. Amin E Moghaddam

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  5. Claire F Pearson

    Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  6. Adam Laing

    Peter Gorer Dept Immunobiology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  7. Lucie Abeler-Dörner

    Peter Gorer Dept Immunobiology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  8. Simon P Forman

    Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  9. Richard K Grencis

    Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  10. Quentin Sattentau

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  11. Anna Katharina Simon

    MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  12. Johanna Pott

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  13. Kevin J Maloy

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    For correspondence
    kevin.maloy@path.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All procedures on mice in this study were conducted in accordance with the UK Scientific Procedures Act (1986) under a project license (PPL 30/2872) authorized by the UK Home Office Animal Procedures Committee and approved by the Sir William Dunn School of Pathology Local Ethical Review Committee.

Reviewing Editor

  1. Ivan Dikic, Goethe University Medical School, Germany

Publication history

  1. Received: October 23, 2015
  2. Accepted: February 23, 2016
  3. Accepted Manuscript published: February 24, 2016 (version 1)
  4. Version of Record published: March 11, 2016 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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