CDld expression on intestinal epithelial cells (IEC) is decreased in inflammatory bowel disease

Abstract

_Background Based upon current thinking, a potential unifying hypothesis to explain IBD pathogenesis is that IBD represents a dysregulated immune response to some component of the luminal bacteria in a genetically susceptible host. It is therefore important to understand the regulation of molecules which may be involved in orchestrating immune responses to bacteria. CDId is a major histocompatibility complex (MHC) class I-like molecule that is expressed on the apical and lateral membranes of IECs and which is predicted to present hydrophobic antigens, such as bacterial lipids, to T cells. We therefore studied CDld expression in patients with IBD. Methods CDld expression was studied in the intestinal specimens obtained from IBD patients by confocal laser microscopy and biochemical methods. Intestinal tissue specimens were frozen and sectioned in OCT compound, stained with CDId specific antibodies and then visualized using confocal laser microscopy. CDld protein expression was studied biochemically in both grossly affected and normal appearing mucosa of IBD patients using immunoprecipitation with CDld specific antibodies in combination with Western blotting. Results: Confocal microscopy imaging showed that, in contrast to normal human intestine, CDId expression was markedly diminished in IBD tissue. Furthermore, differences were observed in specimens obtained from Ulcerative Colitis (UC) and Crohn's disease patients. Specifically, CDld expression was patchy and fragmented in UC and was minimal to absent in patients with Crohn's disease. These findings were corroborated by biochemical studies which showed that not only was CDId markedly decreased to absent in grossly affected bowel specimens of IBD patients but also that CDld expression was moderately reduced in the normal appearing, grossly unaffected bowel of IBD patients. Conclusion Similar to gp 180, a CD66e homologue involved in activation of CD8 ÷ T cells and which may associate with CDId on IECs, expression of CDld is decreased in IBD. Although the consequences of this event are unknown, it is predicted that IBD intestine contains diminished numbers and/or activity of CDld restricted T cells.