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

Kabat, A. M. et al. (2016) The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation. eLife, 5, e12444. (doi: 10.7554/elife.12444) (PMID:26910010) (PMCID:PMC4798959)

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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.

Item Type:Articles
Additional Information:Funding: Wellcome Trust (Graduate Student Scholarship 097112): Agnieszka Martyna Kabat. Wellcome Trust (100290): Simon P Forman, Richard K Grencis. Wellcome Trust (100156): Simon P Forman, Richard K Grencis. Medical Research Council (MR/K011898/1): Johanna Pott, Kevin J Maloy. Wellcome Trust (102972): Kevin J Maloy.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maloy, Professor Kevin
Authors: Kabat, A. M., Harrison, O. J., Riffelmacher, T., Moghaddam, A. E., Pearson, C. F., Laing, A., Abeler-Dorner, L., Forman, S. P., Grencis, R. K., Sattentau, Q., Simon, A. K., Pott, J., and Maloy, K. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:eLife
Publisher:eLife Sciences Publications,
ISSN:2050-084X
ISSN (Online):2050-084X
Published Online:23 February 2016
First Published:First published in eLife 5:e12444
Publisher Policy:Reproduced under a Creative Commons license

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