| First Author | Wang F | Year | 2017 |
| Journal | Endocrinology | Volume | 158 |
| Issue | 6 | Pages | 1951-1963 |
| PubMed ID | 28368514 | Mgi Jnum | J:246086 |
| Mgi Id | MGI:5915059 | Doi | 10.1210/en.2016-1913 |
| Citation | Wang F, et al. (2017) Vitamin D Receptor-Dependent Signaling Protects Mice From Dextran Sulfate Sodium-Induced Colitis. Endocrinology 158(6):1951-1963 |
| abstractText | Low vitamin D status potentiates experimental colitis, but the vitamin D-responsive cell in colitis has not been defined. We hypothesized that vitamin D has distinct roles in colonic epithelial cells and in nonepithelial cells during colitis. We tested this hypothesis by using mice with vitamin D receptor (VDR) deletion from colon epithelial cells (CEC-VDRKO) or nonintestinal epithelial cells (NEC-VDRKO). Eight-week-old mice were treated with 1.35% dextran sulfate sodium (DSS) for 5 days and then euthanized 2 or 10 days after removal of DSS. DSS induced body weight loss and increased disease activity index and spleen size. This response was increased in NEC-VDRKO mice but not CEC-VDRKO mice. DSS-induced colon epithelial damage and immune cell infiltration scores were increased in both mouse models. Although the epithelium healed between 2 and 10 days after DSS administration in control and CEC-VDRKO mice, epithelial damage remained high in NEC-VDRKO mice 10 days after removal of DSS, indicating delayed epithelial healing. Gene expression levels for the proinflammatory, M1 macrophage (M) cytokines tumor necrosis factor-alpha, nitric oxide synthase 2, and interleukin-1beta were significantly elevated in the colon of NEC-VDRKO mice at day 10. In vitro experiments in murine peritoneal Ms demonstrated that 1,25 dihydroxyvitamin D directly inhibited M1 polarization, facilitated M2 polarization, and regulated M phenotype switching toward the M2 and away from the M1 phenotype. Our data revealed unique protective roles for vitamin D signaling during colitis in the colon epithelium as well as nonepithelial cells in the colon microenvironment (i.e., modulation of M biology). |
