Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon.

Détails

ID Serval
serval:BIB_A34545AA75C8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Peyrin-Biroulet L., Beisner J., Wang G., Nuding S., Oommen S.T., Kelly D., Parmentier-Decrucq E., Dessein R., Merour E., Chavatte P., Grandjean T., Bressenot A., Desreumaux P., Colombel J.F., Desvergne B., Stange E.F., Wehkamp J., Chamaillard M.
ISSN
1091-6490[electronic], 0027-8424[linking]
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
107
Numéro
19
Pages
8772-8777
Langue
anglais
Résumé
Crohn's disease (CD), a major form of human inflammatory bowel disease, is characterized by primary immunodeficiencies. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is essential for intestinal homeostasis in response to both dietary- and microbiota-derived signals. Its role in host defense remains unknown, however. We show that PPARgamma functions as an antimicrobial factor by maintaining constitutive epithelial expression of a subset of beta-defensin in the colon, which includes mDefB10 in mice and DEFB1 in humans. Colonic mucosa of Ppargamma mutant animals shows defective killing of several major components of the intestinal microbiota, including Candida albicans, Bacteroides fragilis, Enterococcus faecalis, and Escherichia coli. Neutralization of the colicidal activity using an anti-mDefB10 blocking antibody was effective in a PPARgamma-dependent manner. A functional promoter variant that is required for DEFB1 expression confers strong protection against Crohn's colitis and ileocolitis (odds ratio, 0.559; P = 0.018). Consistently, colonic involvement in CD is specifically linked to reduced expression of DEFB1 independent of inflammation. These findings support the development of PPARgamma-targeting therapeutic and/or nutritional approaches to prevent colonic inflammation by restoring antimicrobial immunity in CD.
Mots-clé
Animals, Bacteria/immunology, Cell Line, Colon/immunology, Colon/microbiology, Crohn Disease/genetics, Crohn Disease/pathology, Fungi/immunology, Gene Expression Regulation, Gene Frequency/genetics, Genotype, Humans, Ileum/immunology, Ileum/microbiology, Immunity, Innate/immunology, Mice, Mice, Inbred C57BL, Models, Immunological, PPAR gamma/deficiency, PPAR gamma/metabolism, Promoter Regions, Genetic/genetics, Protein Binding, beta-Defensins/genetics, beta-Defensins/metabolism
Pubmed
Web of science
Création de la notice
08/03/2011 18:46
Dernière modification de la notice
03/03/2018 20:11
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