Vitamin D acts as pleiotropic immuno-endocrine modulator, regulating immune tolerance, inflammation, and host defense.

Historically, Vitamin D was primarily associated with skeletal biology and calcium-phosphate regulation, crucial for preventing conditions like rickets, osteomalacia, and osteoporosis. However, a significant paradigm shift over the last two decades has established Vitamin D as a pleiotropic immuno-endocrine regulator with systemic relevance far beyond bone health. Its active metabolite, 1,25-dihydroxyvitamin D (calcitriol), binds to the nuclear vitamin D receptor (VDR), which is widely expressed in various immune and endocrine tissues. This broad distribution highlights Vitamin D's integrative role in coordinating immune tolerance, inflammation, and host defense, addressing the gap in understanding its broader systemic impact.

This comprehensive review synthesizes the established understanding of Vitamin D as a crucial immuno-endocrine modulator, moving beyond its historical confinement to skeletal biology. It highlights that the active form, 1,25-dihydroxyvitamin D (calcitriol), binds to the nuclear VDR, which is extensively expressed across various immune cells, including macrophages, dendritic cells (DCs), T cells, and B cells. This widespread VDR distribution enables Vitamin D to regulate key immune processes such as immune tolerance, inflammation, and host defense mechanisms. The paper underscores a significant paradigm shift over the last two decades, recognizing Vitamin D's integrative role in coordinating immune and endocrine signaling, rather than merely acting as a classical micronutrient. > Vitamin D's active metabolite, 1,25-dihydroxyvitamin D, binds to the widely distributed VDR on immune cells and endocrine glands, exerting extensive effects beyond the musculoskeletal system, profoundly impacting immune function.