Influence of Vitamins A and D on the Expression of MicroRNA27-3p Isoforms and GATA3 in Experimental Autoimmune Encephalomyelitis

Vitamins A, D, and microRNAs contribute to T cell differentiation into T(H)2 phenotypes. We investigated the molecular mechanisms and effects of vitamin A and D on the expression of GATA3 and miR-27-3p isoforms in experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis. EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein, mixed with Complete Freund's Adjuvant, together with injection of pertussis toxin. Treatments began one day before immunization with (200 mu g and 100 ng of vitamin A and vitamin D per mouse, respectively, and vitamin A+D (100 mu g+50 ng) per mouse. Expression levels of GATA3 and miR-27-3p isoforms were measured in the CNS and splenocytes by real-time RT-PCR. The expression level of GATA3 in the mice spinal cords and splenocytes was increased in the vitamin A and A+D-treated EAE mice at 24 h and 48 h after restimulation by 10 mu g and 40 mu g of myelin oligodendrocyte glycoprotein. Vitamins A and D and their combination up regulated the miR-27-3p isoforms compared with EAE mice with no treatments. We also demonstrated that miR-273p isoform expression was altered in splenocytes of vitamin-treated EAE mice. The results showed a positive correlation between splenocyte GATA3 levels and miR-27-3p isoform expression. The protective impacts of vitamins A and D in EAE mice may be mediated by the up regulation of GATA3. However, it is not specified whether suppression of GATA3-targeting miRNAs of the miR-27-3p family is involved in this effect. These results do not rule out the possibility that miR27-3p isoforms might have beneficial effects by targeting other transcripts, such as GluA2 and NR2B.