Vitamin D reduces development and progression of virus-induced demyelinating disease (P5131)

Abstract

Abstract Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that is associated with an inflammatory immune response. Microglia are the CNS resident immune cells which have been shown to be activated during MS. Virus infections have been suggested as a causative agent for MS, and vitamin D insufficiency has been correlated with disease development. Thus, we wanted to determine whether higher vitamin D levels at the time of virus infection could alter development of demyelinating disease. Theiler’s murine encephalomyelitis virus (TMEV) induced demyelinating disease is an animal model of MS. TMEV infection of susceptible mice leads to development of a demyelinating disease associated with an inflammatory immune response in the CNS. Our studies showed that increased levels of vitamin D3 at the time of virus infection reduced development and progression of demyelinating disease. Vitamin D reduced the number of CD4+ T cells expressing IFNγ and increased the number of CD25+CD4+ T cells. Most interestingly, vitamin D reduced the expression of pro-inflammatory cytokines and increased the expression of IL-10 and type I interferons by microglia. The reduction in the inflammatory immune response by microglia was dependent on IL-10 induction of SOCS3. Overall, these results show that vitamin D reduced the inflammatory immune response in the CNS and reduced the development and progression of demyelinating disease following virus infection.