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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 AA1, 2
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. Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  4. 4. Department of Clinical Biochemistry, Faculty of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran
  5. 5. Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Veterinary Pathology, Islamic Azad University, Abhar, Iran
  7. 7. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran

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.
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