title: The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation.
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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors.forename: Agnieszka M
authors.initials: AM
authors.lastname: Kabat
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.|Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Harrison
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Riffelmacher
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors.forename: Amin E
authors.initials: AE
authors.lastname: Moghaddam
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
authors.forename: Claire F
authors.initials: CF
authors.lastname: Pearson
authors.affiliation: Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: Laing
authors.affiliation: Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom.
authors.forename: Lucie
authors.initials: L
authors.lastname: Abeler-Dörner
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Forman
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Grencis
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Sattentau
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Anna Katharina
authors.initials: AK
authors.lastname: Simon
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors.forename: Johanna
authors.initials: J
authors.lastname: Pott
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors.forename: Kevin J
authors.identifier: http://orcid.org/0000-0001-5795-7688
authors.initials: KJ
authors.lastname: Maloy
mesh_terms: D000818:Animals; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C532820:Atg16l1 protein, mouse; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins
keywords: IBD; T helper cells; autophagy; immunology; mouse; mucosal immunology