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Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system.

ABSTRACT: Inflammatory bowel disease (IBD) has been attributed to overexuberant host immunity or the emergence of harmful intestinal flora. The transcription factor T-bet orchestrates inflammatory genetic programs in both adaptive and innate immunity. We describe a profound and unexpected function for T-bet in influencing the behavior of host inflammatory activity and commensal bacteria. T-bet deficiency in the innate immune system results in spontaneous and communicable ulcerative colitis in the absence of adaptive immunity and increased susceptibility to colitis in immunologically intact hosts. T-bet controls the response of the mucosal immune system to commensal bacteria by regulating TNF-alpha production in colonic dendritic cells, critical for colonic epithelial barrier maintenance. Loss of T-bet influences bacterial populations to become colitogenic, and this colitis is communicable to genetically intact hosts. These findings reveal a novel function for T-bet as a peacekeeper of host-commensal relationships and provide new perspectives on the pathophysiology of IBD.

SUBMITTER: Garrett WS

PROVIDER: S-EPMC2169385 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system.

Garrett Wendy S WS Lord Graham M GM Punit Shivesh S Lugo-Villarino Geanncarlo G Mazmanian Sarkis K SK Ito Susumu S Glickman Jonathan N JN Glimcher Laurie H LH

Cell 20071001 1

Inflammatory bowel disease (IBD) has been attributed to overexuberant host immunity or the emergence of harmful intestinal flora. The transcription factor T-bet orchestrates inflammatory genetic programs in both adaptive and innate immunity. We describe a profound and unexpected function for T-bet in influencing the behavior of host inflammatory activity and commensal bacteria. T-bet deficiency in the innate immune system results in spontaneous and communicable ulcerative colitis in the absence ...[more]

PMID: 17923086

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Dataset Information

Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system.

Publications

Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system.

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