Format

Send to

Choose Destination
Elife. 2016 Feb 24;5:e12444. doi: 10.7554/eLife.12444.

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

Author information

1
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
2
Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
3
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
4
John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
5
Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
6
Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom.
7
Faculty of Life Sciences, The University of Manchester, 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 characterized 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.

KEYWORDS:

IBD; T helper cells; autophagy; immunology; mouse; mucosal immunology

PMID:
26910010
PMCID:
PMC4798959
DOI:
10.7554/eLife.12444
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center