| First Author | Joshi S | Year | 2011 |
| Journal | Mol Cell Biol | Volume | 31 |
| Issue | 17 | Pages | 3653-69 |
| PubMed ID | 21746882 | Mgi Jnum | J:175072 |
| Mgi Id | MGI:5142338 | Doi | 10.1128/MCB.05020-11 |
| Citation | Joshi S, et al. (2011) 1,25-Dihydroxyvitamin D3 Ameliorates Th17 Autoimmunity via Transcriptional Modulation of Interleukin-17A. Mol Cell Biol 31(17):3653-69 |
| abstractText | A new class of inflammatory CD4(+) T cells that produce interleukin-17 (IL-17) (termed Th17) has been identified, which plays a critical role in numerous inflammatory conditions and autoimmune diseases. The active form of vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], has a direct repressive effect on the expression of IL-17A in both human and mouse T cells. In vivo treatment of mice with ongoing experimental autoimmune encephalomyelitis (EAE; a mouse model of multiple sclerosis) diminishes paralysis and progression of the disease and reduces IL-17A-secreting CD4(+) T cells in the periphery and central nervous system (CNS). The mechanism of 1,25(OH)(2)D(3) repression of IL-17A expression was found to be transcriptional repression, mediated by the vitamin D receptor (VDR). Transcription assays, gel shifting, and chromatin immunoprecipitation (ChIP) assays indicate that the negative effect of 1,25(OH)(2)D(3) on IL-17A involves blocking of nuclear factor for activated T cells (NFAT), recruitment of histone deacetylase (HDAC), sequestration of Runt-related transcription factor 1 (Runx1) by 1,25(OH)(2)D(3)/VDR, and a direct effect of 1,25(OH)(2)D(3) on induction of Foxp3. Our results describe novel mechanisms and new concepts with regard to vitamin D and the immune system and suggest therapeutic targets for the control of autoimmune diseases. |
