Vitamin D as an Immuno-Endocrine Modulator: Discovering Its Role in Autoimmune Disorders and Host Defense Mechanisms

Background/Objectives: Vitamin D, universally recognized for its role in calcium–phosphate homeostasis and skeletal health, has emerged as a key immuno-endocrine modulator. Its active metabolite interacts with the vitamin D receptor (VDR) across immune and endocrine cell populations, influencing gene transcription, cytokine balance, and immune tolerance. This narrative review synthesizes mechanistic, epidemiological, and clinical evidence on the role of vitamin D in immune modulation across autoimmune and infectious diseases. Methods: This narrative review incorporated a structured and comprehensive literature search across PubMed/MEDLINE, Scopus, Web of Science, Embase, and Google Scholar. Results: Vitamin D modulates both innate and adaptive immunity through antimicrobial peptide induction, macrophage and NK cell activation, and promotion of tolerogenic dendritic cells. Clinical and interventional trial outcomes remain heterogeneous and are influenced by baseline vitamin D status, dosing regimens, genetic variability, and disease context. Conclusions: Vitamin D functions in endocrine and immune regulation, contributing to host defense and immune tolerance. Current evidence supports that for autoimmune and infectious conditions, well-designed randomized trials are required to clarify effective dosing, identify responsive subpopulations, and elucidate genetic determinants of therapeutic benefit.