Author/Authors :
Oraei, Mona Department of Immunology - School of Public Health - Tehran University of Medical Sciences, Iran , Bitarafan, Sama Neuroscience Institute -Imam Khomeini Hospital Complex - Iranian Center of Neurological Research Tehran University of Medical Sciences, Iran , Mesbah-Namin, Alireza Department of Clinical Biochemistry - Faculty of Medical Sciences - Tarbiat Modares University, Tehran, Iran , Noori-Zadeh, Ali Department of Clinical Biochemistry - Faculty of Allied Medical Sciences - Ilam University of Medical Sciences, Iran , Mansouri, Fatemeh Department of Immunology - School of Public Health - Tehran University of Medical Sciences, Iran , Parastouei, Karim Department of Cellular and Molecular Nutrition - School of Nutritional Sciences and Dietetic - Tehran University of Medical Sciences, Iran , Anissian, Ali Department of Veterinary Pathology - Islamic Azad University, Abhar, Iran , Yekaninejad, Mir Saeed Department of Epidemiology and Biostatistics - School of Public Health - Tehran University of Medical Sciences, Iran , Hajizadeh, Maryam Department of Parasitology and Mycology - School of Medicine - Iran University of Medical Sciences (IUMS), Tehran, Iran , Saboor-Yaraghi, Ali Akbar Department of Immunology - School of Public Health - Tehran University of Medical Sciences, Iran
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.
Keywords :
Calcitriol , FOXP3 gene , Methylation , Regulatory T-lymphocytes , Vitamin D
