Authors: Suenaert Peter Maerten Philippe Van Assche Gert Van Driessche Willy Geboes Karel Bulteel Veerle Simaels Jeannine Augustijns Patrick Ceuppens Jan L Rutgeerts Paul Perrier Clémentine
Publish Date: 2010/08/01
Volume: 16, Issue: 8, Pages: 1322-1331
Abstract
Peter Suenaert Philippe Maerten Gert Van Assche Willy Van Driessche Karel Geboes Veerle Bulteel Jeannine Simaels Patrick Augustijns Jan L Ceuppens Paul Rutgeerts Clémentine Perrier Effects of T cellinduced colonic inflammation on epithelial barrier function† Inflammatory Bowel Diseases Volume 16 Issue 8 1 August 2010 Pages 1322–1331 https//doiorg/101002/ibd21211Epithelial barrier disturbance is thought to contribute to the pathogenesis of inflammatory bowel diseases however it remains unclear whether it is a primary defect participating to the onset of inflammation or only a consequence of sustained inflammationIn nonreconstituted severe combined immunodeficiency SCID mice no epithelial dysfunction was observed However after transfer of CD4+CD45RBhi T cells or total CD4+ T cells colon of SCID mice displayed a decreased epithelial resistance even before overt microscopic inflammation had occurred Sustained colitis of CD4+CD45RBhi T cell reconstituted mice was also associated with enhanced subepithelial resistance enhanced paracellular permeability and decreased net ion transport All these reflect a disturbance of barrier function and may contribute to diarrhea Epithelial resistance was positively correlated with interleukin 10 IL10 and transforming growth factor β TGFβ levels and net ion transport inversely correlated with tumor necrosis factor alpha TNFα levels pointing to the protective effect of IL10 and TGFβ and to a damaging effect of TNFα Indomethacin a nonselective COX inhibitor decreased epithelial resistance independent of T cells and inflammation but its effect was more pronounced in inflamed colonInduction of colitis by transfer of CD4+CD45RBhi T cells in SCID mice leads to changes in the colonic epithelium before colitis develops Decreased epithelium resistance might contribute to the development of colitis however it is not sufficient to lead to chronic inflammation Inflamm Bowel Dis 2010
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