The Implication of Vitamin D and Autoimmunity: a Comprehensive Review

Abstract

Historically, vitamin D has been associated with the regulation of bone metabolism. However, increasing evidence demonstrates a strong association between vitamin D signaling and many biological processes that regulate immune responses. The discovery of the vitamin D receptor in multiple immune cell lineages, such as monocytes, dendritic cells, and activated T cells credits vitamin D with a novel role in modulating immunological functions and its subsequent role in the development or prevention of autoimmune diseases. In this review we, discuss five major areas in vitamin D biology of high immunological significance: (1) the metabolism of vitamin D; (2) the significance of vitamin D receptor polymorphisms in autoimmune diseases, such as multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; (3) vitamin D receptor transcriptional regulation of immune cell lineages, including Th1, Th17, Th2, regulatory T, and natural killer T cells; (4) the prevalence of vitamin D insufficiency/deficiency in patients with multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; and finally, (5) the therapeutic effects of vitamin D supplementation on disease severity and progression.

Inhibition of Adipogenesis Is Involved in the Protective Effects of 1,25-Dihydroxy Vitamin D3 on the Radiation-Injured Bone Marrow Microenvironment in Mice

“…In addition to regulating calcium and phosphorus homeostasis, this steroid hormone also has a wide range of in vivo biological activities, such as anti-tumor effects and immunoregulation (12,13). In this study, fat vacuoles in the marrow cavity were detected by HE staining.…”

Association between hypovitaminosis D and systemic sclerosis: True or fake?

“…It has an antifibrotic effect on fibroblasts, consequently inhibitingsynthesis and deposition of extracellular matrix [5]. Vitamin D receptor (VDR) signalling is partly responsible for immunoregulating effects on both innate and adaptative immune responses, due to the expression of VDR on the surface of antigen presenting cell (APC), natural killer cells, as well as activated B and T lymphocytes [32,33].…”

“…Concisely, vitamin D acts skewing T cells to Th2 polarization [5,28]; a Th2 cytokine-mediated mechanism could be the native promoting factor responsible for TGFβ activity and profibrotic effects [9,10,28].…”

“…Low vitamin D serum levels are an increasingly described phenomenon worldwide, at least over the last 10-15 years [5,46]. Waterhouse et al in 2009 subordinated low vitamin D levels in autoimmunity to VDR dysfunction and down regulation [36]; then, Pender et al [47] suggested the hormone to represent a major environmentallinked factor promoting Epstein Barr virus (EBV)-induced autoimmune diseases.…”

Vitamin D immunoregulation through dendritic cells

“…An estimated 40–100% of US or European elderly and 1 billion people worldwide do not have sufficient VD3 levels 8. Although severe complications of childhood VD3 deficiency, most notably rickets, are rarely seen nowadays in countries with western lifestyle, the epidemiological associations of autoimmune diseases with VD3 insufficiency point to the importance of a mechanistic understanding of the interactions of the immune system and VD3 8, 9. Clinical trials are currently ongoing, designed to critically evaluate the efficacy of VD3 supplementation in multiple sclerosis (NCT01490502) and Crohn's disease (NCT02208310).…”