The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation
- University of Oxford, United Kingdom
- King's College London, United Kingdom
- The University of Manchester, United Kingdom
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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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.
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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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The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation
eLife 5:e12444.
https://doi.org/10.7554/eLife.12444
