Immunomodulatory Effects of Calcitriol Through Dna Methylation Alteration of Foxp3 in the Cd4+ T Cells of Mice Publisher Pubmed



Oraei M¹ ; Bitarafan S² ; Mesbahnamin SA³ ; Noorizadeh A⁴ ; Mansouri F¹ ; Parastouei K⁵ ; Anissian A⁶ ; Yekaninejad MS⁷ ; Hajizadeh M⁸ ; Sabooryaraghi AA^{1, 2}
Source: Iranian Journal of Allergy# Asthma and Immunology Published:2020

Abstract

Vitamin D plays a variety of physiological functions, such as regulating mineral homeostasis. More recently, it has emerged as an immunomodulator player, affecting several types of immune cells, such as regulatory T (Treg) cells. It has been reported that vitamin D exerts some mediatory effects through an epigenetic mechanism. In this study, the impacts of calcitriol, the active form of vitamin D, on the methylation of the conserved non-coding sequence 2 (CNS2) region of the forkhead box P3 (FOXP3) gene promoter, were evaluated. Fourteen C57BL/6 mice were recruited in this study and divided into two intervention and control groups. The CD4+ T cells were isolated from mice splenocytes. The expression of FOXP3, IL-10, and transforming growth factor-beta (TGF-β1) genes were relatively quantified by real-time PCR technique, and the DNA methylation percentage of every CpG site in the CNS2 region was measured individually by bisulfite-sequencing PCR. Vitamin D Intervention could significantly (p<0.05) increase the expression of FOXP3, IL-10, and TGF-β1 genes in the CD4+ T cells of mice comparing with the control group. Meanwhile, methylation of the CNS2 region of FOXP3 promoter was significantly decreased in three of ten CpG sites in the vitamin D group compared to the control group. The results of this study showed that vitamin D can engage the methylation process to induce FOXP3 gene expression and probably Treg cytokines profile. Further researches are needed to discover the precise epigenetic mechanisms by which vitamin D modulates the immune system. Copyright© October 2020, Iran J Allergy Asthma Immunol. All rights reserved.