Immunomodulatory Effects of Calcitriol through DNA Methylation Alteration of FOXP3 in the CD4+ T Cells of Mice

• Main Authors: Mona Oraei, Sama Bitarafan, Seyed Alireza Mesbah-Namin, Ali Noori-Zadeh, Fatemeh Mansouri, Karim Parastouei, Ali Anissian, Mir Saeed Yekaninejad, Maryam Hajizadeh, Ali Akbar Saboor-Yaraghi
• Format: Article
• Language: English
• Published: Tehran University of Medical Sciences 2020-10-01
• Series: Iranian Journal of Allergy, Asthma and Immunology
• Subjects: Calcitriol; FOXP3 gene; Methylation; Regulatory T-lymphocytes; Vitamin D
• Online Access: https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2772
• ISSN: 1735-1502; 1735-5249

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 significantly (p<0.05) could increase the expression of Foxp3, IL-10, and TGF-β1 gene 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.