Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease

Chu, Hiutung; Khosravi, Arya; Kusumawardhani, Indah P.; Kwon, Alice H. K.; Vasconcelos, A.C.; Cunha, Larissa D.; Mayer, A.; Shen, Yue; Wu, Wei‐Li; Kambal, Amal; Targan, Stephan R.; Xavier, Ramnik J.; Ernst, Peter B.; Green, Douglas R.; McGovern, Dermot; Virgin, Herbert W.; Mazmanian, Sarkis K.

doi:10.1126/science.aad9948

articleScienceMay 6, 2016Closed access

Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease

HCHiutung Chu AKArya Khosravi IPIndah P. Kusumawardhani AHAlice H. K. Kwon AVA.C. Vasconcelos

California Institute of Technology · University of San Diego · +6 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Inflammatory bowel disease (IBD) is associated with risk variants in the human genome and dysbiosis of the gut microbiome, though unifying principles for these findings remain largely undescribed. The human commensal Bacteroides fragilis delivers immunomodulatory molecules to immune cells via secretion of outer membrane vesicles (OMVs). We reveal that OMVs require IBD-associated genes, ATG16L1 and NOD2, to activate a noncanonical autophagy pathway during protection from colitis. ATG16L1-deficient dendritic cells do not induce regulatory T cells (T(regs)) to suppress mucosal inflammation. Immune cells from human subjects with a major risk variant in ATG16L1 are defective in T(reg) responses to OMVs. We propose…

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Topics & keywords

Topics

Keywords

Pathogenesis
Inflammatory bowel disease
Inflammatory Bowel Diseases
Gene
Disease
Immunology
Biology
Computational biology

UN Sustainable Development Goals

Good health and well-being

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