The Autophagy Gene Atg16l1 Differentially Regulates Treg and TH2 Cells to Control Intestinal Inflammation

Overview

Journal Elife

Specialty Biology

Date 2016 Feb 25

PMID 26910010

Citations 98

Authors

Agnieszka M Kabat

Oliver J Harrison

Thomas Riffelmacher

Amin E Moghaddam

Claire F Pearson

Adam Laing

Lucie Abeler-Dorner

Simon P Forman

Richard K Grencis

Quentin Sattentau

Anna Katharina Simon

Johanna Pott

Kevin J Maloy

Affiliations

Soon will be listed here.

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.

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