Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease-Reference-Cited by-同舟云学术

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

Published:2016-05-27 Issue:6289 Volume:352 Page:1116-1120
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Chu Hiutung¹,Khosravi Arya¹,Kusumawardhani Indah P.¹,Kwon Alice H. K.¹,Vasconcelos Anilton C.²,Cunha Larissa D.³,Mayer Anne E.⁴,Shen Yue¹,Wu Wei-Li¹,Kambal Amal⁴,Targan Stephan R.⁵,Xavier Ramnik J.⁶,Ernst Peter B.²,Green Douglas R.³,McGovern Dermot P. B.⁵,Virgin Herbert W.⁴,Mazmanian Sarkis K.¹

Affiliation:

1. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

2. Center for Veterinary Sciences and Comparative Medicine, University of California, San Diego, San Diego, CA 92093, USA.

3. Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.

4. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

5. F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

6. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Abstract

Genes and microbes converge in colitis Both host genetics and intestinal microbes probably contribute to a person's overall susceptibility to inflammatory bowel disease (IBD). The human gut microbe Bacteroides fragilis produces immunomodulatory molecules that it releases via outer membrane vesicles (OMVs). These molecules can protect mice from experimentally induced colitis. Chu et al. now find that OMV-mediated protection from colitis requires Atg16l1 and Nod2 genes whose human orthologs are associated with an increased risk for developing IBD. OMVs trigger an ATG16L1 and NOD2–dependent noncanonical autophagy pathway in dendritic cells (DCs). OMV-primed DCs, in turn, induce regulatory T cells in the intestine that protect against colitis. Science , this issue p. 1116

Funder

National Institutes of Health (NIH)

Ruth L. Kirschtein National Research Service Award

Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute Research Funds

Feintech Family Chair

Wayne and Gladys Valley Foundation

Lupus Research Institute

Lisa Z. Greer Endowed Chair

European Union

Leona M. and Harry B. Helmsley Charitable Trust

NIH

Crohn's and Colitis Foundation of America