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Communicable Ulcerative Colitis Induced by T-bet Deficiency in the Innate Immune System

Garrett, Wendy S. and Lord, Graham M. and Punit, Shivesh and Lugo-Villarino, Geanncarlo and Mazmanian, Sarkis K. and Ito, Susumu and Glickman, Jonathan N. and Glimcher, Laurie H. (2007) Communicable Ulcerative Colitis Induced by T-bet Deficiency in the Innate Immune System. Cell, 131 (1). pp. 33-45. ISSN 0092-8674. PMCID PMC2169385. doi:10.1016/j.cell.2007.08.017. https://resolver.caltech.edu/CaltechAUTHORS:20200309-164448458

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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-α 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.cell.2007.08.017DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169385/PubMed CentralArticle
ORCID:
AuthorORCID
Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2007 Elsevier Under an Elsevier user license. Received 23 April 2007, Revised 9 July 2007, Accepted 13 August 2007, Available online 4 October 2007. We thank D. Hu for expertise in histology and IHC; I. Jackson for assistance in phenotyping and FC; J. Ramirez for his care of our mice; Dr. J. Shim for advice and constructs for luciferase assays; Drs. S. Turley, T. Staton, M. Wein, A. Zullo, A. Kaser, and R. Blumberg for critical reading of the manuscript; Drs. W. Lencer, J. Gordon, D. Peterson, and T. Yatsunenko and members of the Glimcher and Grusby laboratories for helpful discussion. This work was supported by grants from the NIH (CA112663 and AI56296) and an Ellison Scholar Award to L.H.G. W.S.G. is a postdoctoral fellow of the Damon Runyon Cancer Research Foundation and received funding from the Irving Janock Fellowship. G.M.L. was supported by an MRC Clinician Scientist Grant (G108/380) and funding from the Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London, UK. L.H.G. is a member of the Board of Directors of the Bristol-Myers Squib Corporation.
Funders:
Funding AgencyGrant Number
NIHCA112663
NIHAI56296
Ellison Medical FoundationUNSPECIFIED
Damon Runyon Cancer Research FoundationUNSPECIFIED
Irving Janock FellowshipUNSPECIFIED
Medical Research Council (UK)G108/380
Guy's & St Thomas' NHS Foundation TrustUNSPECIFIED
King's College LondonUNSPECIFIED
Subject Keywords:CELLIMMUNO; HUMDISEASE; MICROBIO
Issue or Number:1
PubMed Central ID:PMC2169385
DOI:10.1016/j.cell.2007.08.017
Record Number:CaltechAUTHORS:20200309-164448458
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200309-164448458
Official Citation:Wendy S. Garrett, Graham M. Lord, Shivesh Punit, Geanncarlo Lugo-Villarino, Sarkis K. Mazmanian, Susumu Ito, Jonathan N. Glickman, Laurie H. Glimcher, Communicable Ulcerative Colitis Induced by T-bet Deficiency in the Innate Immune System, Cell, Volume 131, Issue 1, 2007, Pages 33-45, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2007.08.017.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101806
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:10 Mar 2020 14:31
Last Modified:16 Nov 2021 18:06

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