The first 2 authors contributed equally to this work.
Effects of T cell-induced colonic inflammation on epithelial barrier function†
Article first published online: 12 FEB 2010
Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 16, Issue 8, pages 1322–1331, August 2010
How to Cite
Suenaert, P., Maerten, P., Van Assche, G., Van Driessche, W., Geboes, K., Bulteel, V., Simaels, J., Augustijns, P., Ceuppens, J. L., Rutgeerts, P. and Perrier, C. (2010), Effects of T cell-induced colonic inflammation on epithelial barrier function. Inflamm Bowel Dis, 16: 1322–1331. doi: 10.1002/ibd.21211
Supported by grants from the Foundation for Scientific Research Flanders (FWO-Vlaanderen, grant G.0507.06), by a Researcher Fellowship Funding of the Flemish Fund for Scientific Research (FWO-Vlaanderen, grant 1.5.054.02) (to P.S.), by a grant from the Research Council of the Catholic University of Leuven, and by a Schering-Plough IBD fellowship (to P.M., C.P.).
- Issue published online: 13 JUL 2010
- Article first published online: 12 FEB 2010
- Manuscript Accepted: 30 NOV 2009
- Manuscript Received: 18 NOV 2009
- Foundation for Scientific Research Flanders (FWO-Vlaanderen, grant. Grant Number: G.0507.06
- Flemish Fund for Scientific Research (FWO-Vlaanderen, grant. Grant Number: 1.5.054.02
- Research Council of the Catholic University of Leuven
- Schering-Plough IBD fellowship
- Crohn's disease;
- experimental colitis;
- epithelial barrier function;
Epithelial 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 inflammation.
A time course study of epithelial barrier functions and immune mediators was performed in the CD4+CD45RBhi T cell transfer model of colitis using Ussing chambers.
In 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 (IL-10) and transforming growth factor β (TGF-β) levels and net ion transport inversely correlated with tumor necrosis factor alpha (TNF-α) levels, pointing to the protective effect of IL-10 and TGF-β and to a damaging effect of TNF-α. Indomethacin, a nonselective COX inhibitor, decreased epithelial resistance independent of T cells and inflammation, but its effect was more pronounced in inflamed colon.
Induction 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)