Control of autoimmune diseases by the vitamin D endocrine system

Abstract

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D3, is a secosteroid hormone essential for bone and mineral homeostasis. It regulates the growth and differentiation of multiple cell types, and displays immunoregulatory and anti-inflammatory properties. Cells involved in innate and adaptive immune responses—including macrophages, dendritic cells, T cells and B cells—express the vitamin D receptor (VDR), and can both produce and respond to 1,25(OH)2D3. The net effect of the vitamin D system on the immune response is an enhancement of innate immunity coupled with multifaceted regulation of adaptive immunity. Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of several autoimmune diseases, and clarification of the physiological role of endogenous VDR agonists in the regulation of autoimmune responses will guide the development of pharmacological VDR agonists for use in the clinic. The antiproliferative, prodifferentiative, antibacterial, immunomodulatory and anti-inflammatory properties of synthetic VDR agonists could be exploited to treat a variety of autoimmune diseases, from rheumatoid arthritis to systemic lupus erythematosus, and possibly also multiple sclerosis, type 1 diabetes, inflammatory bowel diseases, and autoimmune prostatitis.

Key Points

  • Key cell types in the immune system, including macrophages, dendritic cells, T cells and B cells, express the vitamin D receptor (VDR) and can produce bioactive 1,25(OH)2D3

  • VDR-mediated signaling promotes innate immunity and modulates adaptive immune responses

  • Vitamin D deficiency is associated with increased incidence of autoimmune diseases

  • The anti-inflammatory, protolerogenic, antiproliferative, prodifferentiative, antibacterial, and antiangiogenic properties of VDR agonists offer opportunities for the treatment of autoimmune diseases

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Figure 1: Production of 1,25(OH)2D3 by leukocytes.
Figure 2: Mechanisms involved in the regulation of autoimmune responses by vitamin D receptor agonists.

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Correspondence to Luciano Adorini.

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Competing interests

L Adorini is the cofounder and former Chief Scientific Officer of BioXell and G Penna is an employee of BioXell. L Adorini holds BioXell stock, and L Adorini and G Penna are named as co-inventors on patents held by BioXell.

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Adorini, L., Penna, G. Control of autoimmune diseases by the vitamin D endocrine system. Nat Rev Rheumatol 4, 404–412 (2008). https://doi.org/10.1038/ncprheum0855

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