title: Transgenic Expression of Vitamin D Receptor in Gut Epithelial Cells Ameliorates Spontaneous Colitis Caused by Interleukin-10 Deficiency.
abstract: BACKGROUND
  Vitamin D deficiency is common in patients with inflammatory bowel diseases. The vitamin D receptor (VDR) is a nuclear hormone receptor mediating the activity of vitamin D hormone. Our previous studies showed that intestinal epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this activity is independent of non-epithelial immune VDR actions. Interleukin (IL)-10-deficient mouse is a chronic colitis model that develops colitis due to aberrant immune responses. Here we used IL-10 null (IL-10KO) model to assess the anti-colitic activity of epithelial VDR in the setting of an aberrant immune system.
  
  
  METHODS
  We crossed IL-10KO mice with villin promoter-driven human (h) VDR transgenic (Tg) mice to generate IL-10KO mice that carry the hVDR transgene in intestinal epithelial cells (IL-10KO/Tg). IL-10KO and IL-10KO/Tg littermates were studied in parallel and followed for up to 25 weeks.
  
  
  RESULTS
  By 25 weeks of age, accumulatively 79 % IL-10KO mice developed prolapse, whereas only 40 % IL-10KO/Tg mice did so (P < 0.001). Compared with IL-10KO mice, IL-10KO/Tg littermates showed markedly reduced mucosal inflammation in both small and large intestines, manifested by attenuation in immune cell infiltration and histological damage and a marked decrease in pro-inflammatory cytokine production. IL-10KO/Tg mice also showed reduced intestinal epithelial cell apoptosis as a result of diminished PUMA induction and caspase 3 activation.
  
  
  CONCLUSIONS
  These observations demonstrate that targeting hVDR expression to intestinal epithelial cells is sufficient to attenuate spontaneous colitis caused by an ill-regulated immune system, confirming a critical role of the epithelial VDR signaling in blocking colitis development.
authors.affiliation: Department of Medicine, Division of Biological Sciences, The University of Chicago, 900 E. 57th Street, KCBD 9110, Chicago, IL, 60637, USA.
authors.forename: Maya Aharoni
authors.initials: MA
authors.lastname: Golan
authors.forename: Weicheng
authors.initials: W
authors.lastname: Liu
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Shi
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Jiaolong
authors.initials: J
authors.lastname: Wang
authors.forename: Tianjing
authors.initials: T
authors.lastname: Liu
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Li
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D007249:Inflammation / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*
chemical_list: D018167:Receptors, Calcitriol; D016753:Interleukin-10