Let the sunshine in
Inflammatory bowel disease (IBD) is the collective term for diseases of the bowl, such as ulcerative colitis and Crohn’s disease. Although all aspects of IBD development are not fully understood, a variety of factors, such as genetics, environment, and intestinal microflora composition have been implicated in the disease. Previous studies have identified a link between IBD and vitamin D deficiency, though it is unknown how a lack of vitamin D leads to intestinal inflammation. Weicheng Liu and colleagues at the University of Chicago evaluated the role of vitamin D signaling in the development and prevention of colitis. Evaluation of patients with Crohn’s disease revealed that expression of the vitamin D receptor (VDR) was reduced compared to healthy individuals. In a mouse model of colitis, expression of VDR in the intestine protected animals from the onset of colitis. The authors found that VDR signaling prevented intestinal epithelial cell death thus protecting the mucosal barrier. The above images are immunofluorescent micrographs of the colons of wild type mice (left 2 panels) and VDR transgenic mice (right 2 panels) that were untreated (top 2 panels) or treated with a colitis inducing drug (bottom 2 panels). Loss of epithelial integrity (arrows) as indicated by tight junction staining (red) in drug induced colitis was prevented by VDR expression.
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Abstract
The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn’s disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD4+CD45RBhi T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of
Authors
Weicheng Liu, Yunzi Chen, Maya Aharoni Golan, Maria L. Annunziata, Jie Du, Urszula Dougherty, Juan Kong, Mark Musch, Yong Huang, Joel Pekow, Changqing Zheng, Marc Bissonnette, Stephen B. Hanauer, Yan Chun Li
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ISSN: 0021-9738 (print), 1558-8238 (online)