Vitamin D, Inflammation and Immunity: Review of Literature and Considerations on Recent Translational and Clinical Research Developments
Amelia C. Trombetta, Sabrina Paolino, Maurizio Cutolo
2018
Open Rheumatology Journal
The most relevant and recent literature findings linking exposure to sunlight, Vitamin D (VD), inflammation and immune system in health and disease, are reviewed. Reduced sunlight exposure determined hypo-vitaminosis D to be common among patients or even healthy subjects, especially at higher latitudes. Numerous studies support the hypothesis that VD insufficiency could contribute to the higher autoimmune diseases incidence in the same geographic areas. In the present review, the ways in which
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... D was reported to influence immune system, contributing to organism homeostasis or disease development are addressed. In fact, some of the hormone activities were recognised to determine stimulation or inhibition of immune system components. Several diseases, where an association with VD deficiency was studied, are summarised. Finally, the rationale for optimization of substitutive/additive therapy with VD analogues and the last innovations regarding these drugs are mentioned. Trombetta et al. Relevantly, those are the same regions where the highest prevalence of autoimmune diseases is observed. Likewise, other steroidal hormones, VD3 appear to influence immune responses, in addition to its well-known effect on calcium and bone metabolism [6, 7] . Studies performed in the last twenty years of the past century, on patients with granulomatous diseases, such as sarcoidosis, in which high VD serum levels are present, showed expression of the 25OHD-1-α-hydroxylase enzyme in granulomas forming macrophages [8] . In fact, conversion of 25-OHD to 1,25(OH)D occurs in immune system cells, expressing a different form of 1-α-hydroxylase enzyme and capable of converting the precursor to the active form. The extra-renal enzyme is not regulated by parathyroid hormone, but seems to be induced by cytokines, such as interferon (IFN)-γ, interleukin (IL)-1, or Tumour Necrosis Factor (TNF)-α [9]. Lately, in sarcoidosis, presence of a high number of T regulatory cells (Tregs) was demonstrated, together with the peripheral energy of immune system cells [10]. Interestingly, 1-α-hydroxylase enzyme forms were also described in keratinocytes and consequently, they were considered as a source for autocrine synthesis of 1,25(OH) 2 D [11] . A pleiotropic role for VD3 is supported also by the presence of VD Receptor (VDR) on various cell types, in healthy and diseased tissues like bone marrow, brain, colon, breast, malignant and immune cells [12]. In immune system cells, VDR is present on monocytes and macrophages, dendritic cells, T cells and B cells. Consequently, it was postulated that VD can have, in the periphery, a paracrine or autocrine action, binding on responsive elements (VDRE), located on DNA, and changing the way immune system genes are expressed [13] . Several studies testified the correlation between acquired VD deficiency and reduced immune function or autoimmunity development, cancer and even cardiovascular diseases [14 -18]. Also, the potential for confounding factors was investigated, since the presence of a systemic inflammatory response was reported to be associated with lower levels of micronutrients like albumin or lipid soluble vitamins, in plasma [19]. Vd and Innate Immunity VD has both stimulatory and inhibitory effects on innate immune cells. Macrophages, monocyte-derived dendritic cells (DCs) and dermal DCs own the whole enzyme supply needed to convert VD3 into 1,25(OH) 2 VD3 Figs. (1 and 2) [20, 21]. Fig. (1) . Cell-to cell interactions in immune responses modulated by VD.
doi:10.2174/1874312901812010201
fatcat:62habf34hzaapbixegoylc3hci