Regulatory Role of Vitamin D and Its Derivatives in the Immune System

Dear Colleagues,

During the last three decades, scientific breakthroughs in laboratory investigations and clinical medicine have revealed new biological functions of vitamin D that are of high importance for human health, and that are closely connected with the immuno-regulatory effects of this seco-steroid hormone. One hallmark was the detection of vitamin D receptors (VDRs) in a broad variety of cell types and tissues that are not associated with the regulation of calcium homeostasis, including activated human macrophages and many other immunoregulatory cells. Another important scientific breakthrough was the recent identification of alternate non-classical vitamin D pathways that are not mediated by the activation of VDRs via the binding of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the classical active form of vitamin D. In contrast, these new pathways exert their effects at least in part via the binding of several endogenously produced vitamin D hydroxy-metabolites to alternate receptors, including retinoid orphan receptors (RORs), the aryl hydrocarbon receptor (AhR) and liver X receptors (LXRs). With AhR having been identified as an immune and bacteria sensor receptor that controls inflammation, these alternate vitamin D pathways are of high importance for the immune system. In summary, a large body of laboratory investigations have now demonstrated that vitamin D is a key factor regulating both innate and adaptive immunity. These laboratory investigations provide convincing supportive evidence for clinical studies in translational medicine that have recently targeted the vitamin D endocrine system as a promising tool for the pharmacological prevention and treatment of a broad variety of pathological inflammatory conditions, including allergies, infections and many autoimmune diseases. This Special Issue of Nutrients summarizes our present understanding of the role of vitamin D for the immune system. We give an outlook on present concepts and future directions of this hot topic that have now opened many new promising research avenues for clinical and laboratory research. 

Prof. Dr. Jörg Reichrath
Prof. Dr. Andrzej Slominski
Dr. Michael F. Holick
Guest Editors

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