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Vitamins a and D Enhance the Expression of Ror-Γ-Targeting Mirnas in a Mouse Model of Multiple Sclerosis Publisher Pubmed



Mohammadikordkhayli M1, 2 ; Sahraian MA3 ; Ghorbani S2 ; Mansouri F1 ; Talebi F4 ; Noorbakhsh F5 ; Sabooryaraghi AA1
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, AB, Canada
  3. 3. Sina MS Research Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Immunoregulation Research Center, Shahed University, Tehran, Iran
  5. 5. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Molecular Neurobiology Published:2023


Abstract

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 γ-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 γ-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 γ-t. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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