ABSTRACT
Multiple sclerosis (MS) is a complex inflammatory and demyelinating disease of the central nervous system (CNS) frequently starts in young adulthood. Demyelination, inflammatory and axonal damage in the CNS is the pathological hallmark of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. 1, 25-dihydroxyvitamin D3 (Vitamin D3) is involved in calcium regulation, phosphorus homeostasis, and bone mineralization. In addition, vitamin D3 has potential inhibitory effects on immune cells in various inflammatory and autoimmunity disease.
C57BL/6 female mice were divided into prevention groups (low, middle and high doses) and treatment groups (middle and high doses). Prevention groups received vitamin D3 2 weeks before EAE induction, and treatment groups were treated with vitamin D3 simultaneous with EAE induction. Vitamin D3 inhibits the development of EAE in a dose-dependent manner. Histological studies revealed reduced demyelination and limited infiltration into CNS, moreover vitamin D3 increased the production of IL-4, IL-10, and TGF-β, while a significant reduction in the production of IFN-γ, IL-6, TNF-α, and IL-17 was observed. Flow cytometry results for CD4+ T cell subsets in compliance with ELISA cytokine assay results showed a significant decrease in the percentage of Th1 and Th17, but also a significant increase in the percentage of Th2 and Treg for middle and high dose vitamin D3 treated mice. Real-time PCR results indicated that middle and high dose vitamin D3 treatment reduced T-bet and ROR-γt expression, but enhanced GATA3 and Foxp3 expression. Real-Time PCR results in CNS for T cell subsets related cytokines and transcription factors supported the results of flow cytometry and ELISA. This study indicated that middle and high doses of vitamin D3 deviate the balance between Th1/Th2 and Th17/Treg to Th2 and Treg. Moreover, vitamin D3 could reduce the incidence and severity of EAE clinical disease.
Acknowledgments
The authors would like to thank the authorities in research council of Mashhad University of Medical Sciences (MUMS) for their financial support (Grant numbers 901064).
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No potential conflict of interest was reported by the authors.
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Notes on contributors
Dariush Haghmorad
Dariush Haghmorad is a faculty member in Semnan University of Medical Sciences. He has a PhD in Medical Immunology from Mashhad University of Medical Sciences.
Esmaeil Yazdanpanah
Esmaeil Yazdanpanah has a MSc in Immunology from Mashhad University of Medical Sciences.
Maryam Jadid Tavaf
Maryam Jadid Tavaf Simin Zargaranib and Azita Soltanmohammadi are MSc Immunology students in Semnan University of Medical Sciences.
Simin Zargarani
Mohammad Bagher Mahmoudi is worked in Research &Development Department, ROJE Technologies, Yazd, Iran. He has a MSc degree in Genetic from Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Azita Soltanmohammadi
Mahmoud Mahmoudi is a professor of immunology in Mashhad University of Medical Sciences. He is a head of Department of Immunology and Allergy.