Abstract
Experimental allergic encephalomyelitis (EAE) is a Th1 cell‐mediated autoimmune disease model of multiple sclerosis (MS). Vitamin D deficiency is commonly observed in MS patients and vitamin D supplements reduce the clinical symptoms of EAE and MS. Earlier studies have shown that in vivo treatment with vitamin D analogs ameliorates EAE in association with the inhibition of IL‐12 production and Th1 differentiation. The mechanisms in the regulation of Th1 response by vitamin D in EAE/MS are, however, not known. We show that in vivo treatment of C57BL/6 and SJL/J mice (i.p.) with 100 ng of 1,25 dihydroxyvitamin D3, on every other day from Day 0–30, ameliorates EAE in association with the inhibition of IL‐12 production and neural antigen‐specific Th1 response. In vitro treatment with 1,25(OH)2D3 inhibited IFNγ‐induced tyrosine phosphorylation of STAT1, without affecting JAK2, in EOC‐20 microglial cells. Treatment of activated T cells with 1,25(OH)2D3 also inhibited the IL‐12‐induced tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4 in association with a decrease in T cell proliferation in vitro. These findings highlight the fact that vitamin D modulates JAK‐STAT signaling pathway in IL‐12/IFNγ axis leading to Th1 differentiation and further suggest its use in the treatment of MS and other Th1 cell‐mediated autoimmune diseases. © 2006 Wiley‐Liss, Inc.