Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential

Abstract

Over the last three decades, it has become clear that the role of vitamin D goes beyond the regulation of calcium homeostasis and bone health. An important extraskeletal effect of vitamin D is the modulation of the immune system. In the context of autoimmune diseases, this is illustrated by correlations of vitamin D status and genetic polymorphisms in the vitamin D receptor with the incidence and severity of the disease. These correlations warrant investigation into the potential use of vitamin D in the treatment of patients with autoimmune diseases. In recent years, several clinical trials have been performed to investigate the therapeutic value of vitamin D in multiple sclerosis, rheumatoid arthritis, Crohn’s disease, type I diabetes, and systemic lupus erythematosus. Additionally, a second angle of investigation has focused on unraveling the molecular pathways used by vitamin D in order to find new potential therapeutic targets. This review will not only provide an overview of the clinical trials that have been performed but also discuss the current knowledge about the molecular mechanisms underlying the immunomodulatory effects of vitamin D and how these advances can be used in the treatment of autoimmune diseases.

The role and mechanism of vitamin D‐mediated regulation of Treg/Th17 balance in recurrent pregnancy loss

“…34,47 This study showed that a rather high proportion of RPL patients have vitamin D deficiency compared with women with NP, consistent with previous studies. 34,47 This study showed that a rather high proportion of RPL patients have vitamin D deficiency compared with women with NP, consistent with previous studies.…”

“…The immunomodulatory function of vitamin D in immune-related diseases has garnered increasing attention, including in the case of maternal fetal immune imbalance diseases, which contribute to RPL. 34,47 This study showed that a rather high proportion of RPL patients have vitamin D deficiency compared with women with NP, consistent with previous studies. 44,48,49 A prospective cohort study of 1191 women showed an association between sufficient preconception levels of 25(OH)D 3 (≥75 nmol/L) and increased rate of pregnancy and live birth.…”

“…Vitamin D, which plays a key physiological role in critical functions of calcium and phosphorus metabolism, is synthesized in the skin and taken from food. 34,35 Low or insufficient vitamin D status, mainly that of circulating 25(OH)D 3 , has been associated with disease prevalence and severity. 33 The actions of 1,25(OH) 2 D 3 are mediated through its specificity and high affinity for the vitamin D receptor (VDR), which is a member of the nuclear receptor family.…”

“…33 The actions of 1,25(OH) 2 D 3 are mediated through its specificity and high affinity for the vitamin D receptor (VDR), which is a member of the nuclear receptor family. 34,35 Low or insufficient vitamin D status, mainly that of circulating 25(OH)D 3 , has been associated with disease prevalence and severity. 36 Vitamin D is thought to be an immunosuppressive agent, a concept that has evolved to include the regulation of immune tolerance and homeostasis.…”

Vitamin D receptor and STAT3 cooperate to establish TET2-mediated tolerogenesis

“…Vitamin D supplementation is generally used as a preventive agent or a co-adjuvant for diseases with underlying autoimmune or pro-inflammatory states (Bscheider and Butcher, 2016;Dankers et al, 2017). DCs represent an excellent target of vitamin D to dampen autoimmunity and inflammation, not only because these myeloid cells express the whole set of enzymes to generate the active form of vitamin D (Mora et al, 2008) but also for their unique role as initiators of immune responses.…”