University of Groningen Human mucosal IgA in health and disease

Both the role of inducible nitric oxide synthase (iNOS) in the development of inflammatory bowel disease (IBD) as well as the molecular details governing its mucosal induction remain unclear. In the present study we evaluated the role of the residing intestinal microflora in the induction of epithelial iNOS upon transfer of CD45RB CD4 T cells to SCID mice. To this end, CB-17 SCID mice were reared with conventional flora (CNV) or germfree CB-17 SCID mice were monoassociated with Helicobacter.muridarum, act A (-) mutant L. monocytogenes, segmented filamentous bacteria (SFB), or O. anthropi. Within 2 weeks CNV SCID mice injected with CD45RB CD4 T cells showed a focal, epithelial iNOS expression on the apical site of villi that preceded the infiltration of CD4 cells and cytokine production followed by extension of this expression to the entire surface along the whole crypt axis as the colitis progressed. SCID mice monoassociated with H.muridarum developed a severe colitis and showed high epithelial iNOS expression. CNV-SCID mice without T cells and SCID mice mono-associated with SFB did not show any iNOS expression, whereas SCID mice mono-associated with act A(-) mutant Listeria. monocytogenes and Ochrobactrum. anthropi showed some scattered epithelial iNOS staining on the apical site of a few villi, but none of these mice developed colitis. These findings demonstrate that the expression of epithelial iNOS is highly bacterium-specific and correlates with the severity of disease, suggesting an important role for this enzyme in the development of IBD. Epithelial iNOS expression in the CD45RB transfer model of colitis 103 5.