MiRNA-29b modulates neuroinflammation by targeting T-bet in Experimental Autoimmune Encephalomyelitis mice treated with vitamins A and D

Abstract

Abstract Objective: Vitamins A and D are modulators of inflammatory responses, and their deficiency is associated with autoimmune diseases including multiple sclerosis (MS). we investigated the correlation between treatment with vitamins A/D, differentiation of Th1 cells in EAE mice and the role of miR-29a/b. Methods: EAE was induced in C57BL/6 mice. Animals were treated with vitamin A, D and A+D. We measured the expression of miRNAs and their target genes in the CNS and lymphocytes of treated mice by RT-PCR. Th1 cell Percentages was measured in splenocytes utilizing intracellular staining and flow cytometry. To examine the role of miRNAs in leukocyte differentiation and function, miR-29b mimic sequences were transfected into cultured purified CD4+ T cells which analyzed by flow cytometry. Results: The expression levels of T-bet reduced and increased levels of miR-29a/b-3p in the spinal cords and splenocytes of vitamin A and D treated EAE mice compared with EAE mice. The percentage of Th1 cells decreased in splenocyte from mice treated with vitamins A and D. miR-29b mimic sequences suppressed Th1 production in CD4+ T cells. Conclusion: A and D diminish neuroinflammation in EAE by increasing the expression of miR-29b-3p, which acts as an inhibitor of CD4+ T cell differentiation to IFN-γ-producing Th1 cells.