Vitamins A and D Enhance the Expression of Ror-& gamma;-Targeting miRNAs in a Mouse Model of Multiple Sclerosis

Autoreactive T cells, particularly those characterized by a Th17 phenotype, exert significant influence on the pathogenesis of multiple sclerosis (MS). The present study aimed to elucidate the impact of individual and combined administration of vitamin A and D on neuroinflammation, and microRNAs (miRNAs) involved in T helper (Th)17 development, utilizing a murine model of experimental autoimmune encephalomyelitis (EAE). EAE was induced in C57BL/6 mice, and 3 days prior to immunization, intraperitoneal injections of vitamins A and D or their combination were administered. Th17 cell percentages were determined in splenocytes utilizing intracellular staining and flow cytometry. Furthermore, the expression of Ror & gamma;-t, miR-98-5p and Let-7a-5p, was measured in both splenocytes and spinal cord tissues using RT-PCR. Treatment with vitamin A and D resulted in a reduction in both disease severity in EAE mice. Treated mice showed a decreased frequency of Th17 cells and lower expression levels of IL17 and Ror & gamma;-t in splenocytes and spinal cord. The spinal cord tissues and splenocytes of mice treated with vitamins A, D, and combined A+D showed a significant upregulation of miR-98-5p and Let-7a-5p compared to the EAE group. Statistical analysis indicated a strong negative correlation between miR-98-5p and Let-7a-5p levels in splenocytes and Ror-t expression. Our findings indicate that the administration of vitamins A and D exerts a suppressive effect on neuroinflammation in EAE that is associated with a reduction in the differentiation of T cells into the Th17 phenotype and is mediated by the upregulation of miR-98-5p and Let-7a-5p, which target the Ror & gamma;-t.

Automated summary

This study aimed to investigate the impact of individual and combined administration of vitamin A and D on neuroinflammation and microRNAs associated with Th17 development in a murine model of experimental autoimmune encephalomyelitis (EAE). The results showed that treatment with vitamin A and D reduced disease severity in EAE mice, decreased Th17 cell frequency, and lowered expression levels of IL17 and Rorγt. Furthermore, the expression levels of miR-98-5p and Let-7a-5p were significantly upregulated in splenocytes and spinal cord tissues of mice treated with vitamins A, D, and A+D. These findings suggest that the administration of vitamins A and D suppresses neuroinflammation in EAE by reducing Th17 differentiation, which is mediated by the upregulation of miR-98-5p and Let-7a-5p targeting Rorγt.