ReviewVitamin D endocrine system involvement in autoimmune rheumatic diseases
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
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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.
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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).
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Major
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