Epigenetic Influences of Vitamin D on Immune System Development in Early Life

Vitamin D plays an important immunomodulatory role during early life, influencing the programming of the developing immune system through molecular and epigenetic mechanisms. Emerging evidence suggests that the active form of vitamin D, calcitriol, regulates gene expression by binding to the vitamin D receptor (VDR) and modifying epigenetic marks such as DNA methylation, histone acetylation, and microRNA expression. These mechanisms influence key immune regulatory genes including FOXP3, IL-4, and IL-10, thereby promoting regulatory T-cell development and maintaining the balance between Th1 and Th2 immune responses during infancy. Maternal and neonatal vitamin D deficiency may disrupt these epigenetic processes, potentially predisposing infants to infections, allergic diseases, and immune dysregulation later in life. Understanding these mechanisms may provide insights into the long-term effects of early-life vitamin D status on immune health and susceptibility to inflammatory and autoimmune diseases. These findings underscore the potential of vitamin D as a modifiable factor in early-life nutritional interventions and preventive healthcare strategies. This review highlights the molecular and epigenetic pathways through which vitamin D shapes immune development in early life, with a focus on vitamin D receptor–mediated transcriptional regulation and its impact on immune-metabolic interactions. Additionally, the role of vitamin D in influencing key immune pathways such as Th1/Th2 balance and inflammatory responses is discussed. This review summarizes current evidence on the molecular epigenetic pathways through which vitamin D shapes infant immune development and highlights the potential implications for early-life immune programming and disease prevention.