Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

Abstract

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

Keywords: Addison’s disease; antiphospholipid syndrome; autoimmune diseases; autoimmune liver disease; autoimmune thyroid disease; autoimmunity; rheumatoid arthritis; spondyloarthritis; systemic lupus erythematosus; type 1 diabetes mellitus; vitamin D.

Figure 1

Scheme of 1α,25(OH)2D3 role in regulating immune response. As reviewed, it interacts both with innate- and adaptive-immune cells and with resident synoviocytes as well as osteoclasts, resulting in a decrease of synovial inflammation and, finally, in bone erosion. Arrows are used to illustrate decreased (↓) or increased (↑) production of specific actions, cells or molecules.

Figure 2

Hashimoto’s thyroiditis (HT) is a T-cell-mediated endocrine autoimmune disease. Patients harbor higher thyroid peroxidase antibodies (TPOAb) and TgAb serum levels and thyroid intraglandular infiltration of B and T lymphocytes with CD4+ Th1 subtype predominance. Graves’ disease (GD) is characterized by a prominent Th2-mediated humoral response, which induce the expression of stimulatory antibodies. Vitamin D is able to reduce the proliferation and differentiation of B cells into plasma cells and induce the apoptotic cascade of immunoglobulin. In this context, vitamin D inhibits the Th1 cells proliferation as well as the Th1-mediated cytokines production (IL-2, IFN-γ, and TNFα) and modulates Th2 cells and cytokines production (IL-4, IL-5, and IL-10) inducing Th2 phenotype. Arrows are used to illustrate decreased (↓) or increased (↑) production of specific actions, cells or molecules.