Vitamin D, Autoimmune Disease and Rheumatoid Arthritis

Abstract

Vitamin D has been reported to influence physiological systems that extend far beyond its established functions in calcium and bone homeostasis. Prominent amongst these are the potent immunomodulatory effects of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-(OH) 2 D3). The nuclear vitamin D receptor (VDR) for 1,25-(OH) 2 D3 is expressed by many cells within the immune system and resulting effects include modulation of T cell phenotype to suppress pro-inflammatory Th1 and Th17 CD4+ T cells and promote tolerogenic regulatory T cells. In addition, antigen-presenting cells have been shown to express the enzyme 1α-hydroxylase that converts precursor 25-hydroxyvitamin D3 (25-OHD3) to 1,25-(OH) 2 D3, so that immune microenvironments are able to both activate and respond to vitamin D. As a consequence of this local, intracrine, system, immune responses may vary according to the availability of 25-OHD3, and vitamin D deficiency has been linked to various autoimmune disorders including rheumatoid arthritis (RA). The aim of this review is to explore the immune activities of vitamin D that impact autoimmune disease, with specific reference to RA. As well as outlining the mechanisms linking vitamin D with autoimmune disease, the review will also describe the different studies that have linked vitamin D status to RA, and the current supplementation studies that have explored the potential benefits of vitamin D for prevention or treatment of RA. The overall aim of the review is to provide a fresh perspective on the potential role of vitamin D in RA pathogenesis and treatment.

Editorial: Immune-Modulatory Effects of Vitamin D

“…At the cellular level, vitamin D exerts anti-inflammatory effects on immune cells that express the vitamin D receptor (VDR) such as monocytes, macrophages, and T lymphocytes, which in turn shapes the immune response during the onset of inflammation and infection and following vaccination. Vitamin D exerts anti-inflammatory effects by reducing pro-inflammatory cytokines production from macrophages and T cells ( 12 , 13 ). Carlberg eloquently demonstrated that vitamin D/VDR signaling impacts chromatin modeling leading to significant modification of human monocytes epigenome during perturbation, consequently reducing cytokine release and modulating trained innate immunity.…”

“…To confirm the inhibitory effect of VDR on NLP3 inflammasome activation, authors used VDR-deficient mice and showed that IL-1β release was significantly reduced in vivo confirming that VDR inhibited NALP3 inflammasome activation. Vitamin D deficiency is associated with bone pain in particular and chronic disease pain in general ( 12 , 14 ). The proposed mechanisms by which Vitamin D/VDR signaling modulate pain sensation is reviewed by Habib et al .…”

“…Sufficient levels of vitamin D have been shown to regulate T cell proliferation by controlling T cell antigen receptor and T cell activation as well as enhancing the phagocytic activity of macrophages ( 12 , 14 ). The immune suppressive effects of regulatory T cells (T-reg) in controlling inflammation and preventing autoimmunity is well-established.…”

“…Therefore, vitamin D exerts various immune modulatory effects during autoimmune diseases. Another example of autoimmune diseases is Type 1 diabetes mellitus (T1DM) where insulin producing pancreatic β-cells are attacked by T cell-mediated autoimmunity ( 12 , 16 ). Stem cell transplantation has emerged as regenerative treatment for T1DM as it possess immune suppressive potential.…”

Vitamin D in Musculoskeletal Health and Beyond

“…The potential immunomodulatory effects of vitamin D in vitro are well recognised and Harrison et al describe their potential impact in vivo, particularly in rheumatoid arthritis [12]. They present a delightfully clear figure reminding the reader of the immune mechanisms under consideration.…”