Elsevier

Autoimmunity Reviews

Volume 11, Issue 2, December 2011, Pages 84-87
Autoimmunity Reviews

Review
Vitamin D endocrine system involvement in autoimmune rheumatic diseases

https://doi.org/10.1016/j.autrev.2011.08.003Get rights and content

Abstract

Vitamin D is synthesized from cholesterol in the skin (80–90%) under the sunlight and then metabolized into an active D hormone in liver, kidney and peripheral immune/inflammatory cells. These endocrine-immune effects include also the coordinated activities of the vitamin D-activating enzyme, 1alpha-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) on cells of the immune system in mediating intracrine and paracrine actions. Vitamin D is implicated in prevention and protection from chronic infections (i.e. tubercolosis), cancer (i.e. breast cancer) and autoimmune rheumatic diseases since regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions). Vitamin D has modulatory effects on B lymphocytes and Ig production and recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis. A circannual rhythm of trough vitamin D levels in winter and peaks in summer time showed negative correlation with clinical status at least in rheumatoid arthritis and systemic lupus erythematosus.

Recently, the onset of symptoms of early arthritis during winter or spring have been associated with greater radiographic evidence of disease progression at 12 months possibly are also related to seasonal lower vitamin D serum levels.

Section snippets

Vitamin D is a steroid hormone

Both genetic and environmental factors affect prevalence of autoimmune disturbances and are involved in the altered neuroendocrine immune response that characterize several autoimmune rheumatic diseases [1]. Therefore, the fact that vitamin D (1,25(OH)2D3 ) as a true steroid hormone (common structure with glucocorticoids, since both synthesized from cholesterol) has been implicated in the pathogenesis of different autoimmune diseases, suggests that vitamin D endocrine system might be one of the

Vitamin D, innate immunity and seasonality of rheumatoid arthritis

Vitamin D, via its active hormonal metabolite 1,25(OH)2D3, regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions) (Fig. 1)[11].

Potentiation of the innate immune response at surfaces exposed to the environment provides a first line of defense against pathogens, and so would be expected to enhance resistance to acute infections in

Vitamin D, adaptive immunity and rheumatoid arthritis

By considering in a more detailed manner the effects on the adaptive immune response, vitamin D mainly downregulates Th1-dependent responses such as in RA (Fig. 1)[23].

Although T cell polarization can indirectly be affected by 1,25(OH)2D3 induced altered APC cytokine expression, it is becoming clear that T cells including Th17 cells are direct 1,25(OH)2D3 targets (Fig. 1) [24], [25]. In human T cells, vitamin D suppresses IL-17A and IFN-γ production and stimulates IL-4 and IL-10 production [26]

Vitamin D, B cells and systemic lupus erythematosus

Vitamin D has modulatory effects also on B lymphocytes and Ig production (Fig. 1). Recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis [29]. In addition, to confirming direct VDR-mediated effects on B cell proliferation and Ig production, a recent study also highlighted the ability of 1,25(OH)2D3 to inhibit the differentiation of plasma cells and class switched memory cells, suggesting a potential role for vitamin D in B cell-related

Possible inhibition of cell growth via aromatase inhibition by 1,25(OH)2D3

Aromatase, is the enzyme that catalyzes estrogen synthesis from androgenic precursors and its expression in the breast is critical for the progression of ER-positive breast cancer (BCa) in postmenopausal women [36].

Interestingly, 1,25(OH)2D3 regulates the expression of aromatase in a tissue-selective manner and a recent study revealed that 1,25(OH)2D3 significantly decreases aromatase expression by a direct transcriptional repression of promoter II/I.3 in human BCa cells and a cell culture

Take-home messages

  • Vitamin D is a true steroid hormone having a common structure with glucocorticoids, since both are synthesized from cholesterol, and being metabolized into active D hormone in liver, kidney and peripheral cells.

  • Vitamin D, via its active hormonal metabolite 1,25(OH)2D3, regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions).

  • Major

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