• The Role of Vitamin D in the Immune System and Autoimmune Diseases
  • fateme jafari,1,* Shaghayegh Sharifi,2
    1. Department of Medical Sciences, Gorgan Branch, Islamic Azad University, Iran
    2. Department of Basic Science, Rasht Branch, Islamic Azad University


  • Introduction: Introduction: recent systematic review reached the conclusion that several studies performed over the last 40 years support the role of vitamin D in the prevention of autoimmune diseases but that there is still a lack of randomized controlled clinical trials in this field although Different disease outcomes are observed in treatment with vitamin D as high inter-individual difference is present with complex gene expression in human peripheral blood mononuclear cellsBeyond its well-established role in calcium and bone homeostasis, vitamin D also plays a critical part in regulating both innate and adaptive immune responses. Deficiency of vitamin D is commonly observed in autoimmune diseases
  • Methods: Mathods: A comprehensive literature search was conducted across multiple electronic databases, including PubMed, ScienceDirect, Google Scholar, Scopus, MDPI, ProQuest, and PLOS ONE. The search strategy was developed using the primary keywords “vitamin D,” “autoimmune disease,” and “immune system,” in combination with relevant Medical Subject Headings (MeSH) to ensure broader coverage of related terms such as “cholecalciferol” and “vitamin D deficiency.” Boolean operators were applied where appropriate to refine the search results. The search was restricted to review and original research articles published in English between May 2013 and April 2025. After removing duplicates, the remaining articles were screened by title, abstract, and full text according to predefined inclusion and exclusion criteria.
  • Results: Result: The literature consistently demonstrates that vitamin D, particularly its active metabolite 1,25-dihydroxycholecalciferol (calciferol), plays a central role in immune regulation. Vitamin D enhances both innate and adaptive immunity by activating T and B lymphocytes, macrophages, and dendritic cells, while increasing the production of antimicrobial peptides and neutralizing antibodies. Vitamin D deficiency is associated with immune dysregulation and increases susceptibility to autoimmune diseases, including multiple sclerosis, type 1 diabetes, Hashimoto’s thyroiditis, Sjögren’s syndrome, and autoimmune cytopenias. Low serum 25(OH)D levels are also correlated with greater disease severity and higher morbidity in respiratory infections such as influenza and COVID-19. Mechanistically, vitamin D suppresses the production of inflammatory cytokines IL-12 and IL-23 by dendritic cells, reduces Th1 differentiation and inflammatory cytokine secretion (IL-2, IFN-γ, TNF-α), while promoting Th2 and regulatory T cell differentiation, anti-inflammatory cytokine production (IL-4, IL-5, IL-10), and FoxP3 transcription factor expression. Additionally, vitamin D deficiency induces cytotoxic skewing of TH2 cells, representing a novel paradigm in autoimmune pathogenesis.
  • Conclusion: Conclusion: Collectively, these findings highlight that maintaining adequate circulating 25(OH)D levels is essential for normal immune function and prevention of autoimmune diseases. Vitamin D exerts multifaceted protective effects by modulating T and B lymphocyte activity, dendritic cell function, and cytokine profiles. Its deficiency not only exacerbates existing autoimmune diseases but also increases susceptibility to new autoimmune manifestations and infectious complications. Ensuring sufficient vitamin D status through supplementation, diet, or lifestyle interventions may therefore reduce disease severity, prevent autoimmune dysregulation, and improve overall health outcomes. Further research into the role of vitamin D in immune cell plasticity and disease-specific mechanisms may provide novel therapeutic targets for autoimmune conditions.
  • Keywords: Keywords: cholecalciferol . vitamin D . immune system . autoimmune disease