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1.
Mucosal vitamin D signaling in inflammatory bowel disease.
Kellermann, L, Jensen, KB, Bergenheim, F, Gubatan, J, Chou, ND, Moss, A, Nielsen, OH
Autoimmunity reviews. 2020;(11):102672
Abstract
Epidemiological studies have identified vitamin D (25(OH)D) deficiency to be highly prevalent among patients with inflammatory bowel disease (IBD), and low serum levels correlate with a higher disease activity and a more complicated disease course. The link to IBD pathogenesis has been subject of investigations, primarily due to the distinct immunological functions of vitamin D signaling, including anti-inflammatory and anti-fibrotic actions. Vitamin D is a pleiotropic hormone that executes its actions on cells through the vitamin D receptor (VDR). A leaky gut, i.e. an insufficient intestinal epithelial barrier, is thought to be central for the pathogenesis of IBD, and emerging data support the concept that vitamin D/VDR signaling in intestinal epithelial cells (IECs) has an important role in controlling barrier integrity. Here we review the latest evidence on how vitamin D promotes the interplay between IECs, the gut microbiome, and immune cells and thereby regulate the intestinal immune response. On the cellular level, vitamin D signaling regulates tight junctional complexes, apoptosis, and autophagy, leading to increased epithelial barrier integrity, and promotes expression of antimicrobial peptides as part of its immunomodulating functions. Further, intestinal VDR expression is inversely correlated with the severity of inflammation in patients with IBD, which might compromise the positive effects of vitamin D signaling in patients with flaring disease. Efforts to reveal the role of vitamin D in the pathophysiology of IBD will pave the road for the invention of more rational treatment strategies of this debilitating disease in the future.
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2.
Vitamin D in trichology: a comprehensive review of the role of vitamin D and its receptor in hair and scalp disorders.
Damiani, G, Conic, R, Orlando, G, Zampetti, A, Marinello, E, Piai, M, Linder, MD
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2020;(2):190-197
Abstract
Vitamin D plays an important role in maintaining the homeostasis of various biological systems. Beside its well-known function in calcium and phosphate metabolism, it plays a major role in pathophysiology of skin and adnexa. Indeed, vitamin D, through its receptor (VDR), decreases keratinocyte proliferation, improves their differentiation and modulates both cutaneous innate (antimicrobial activity and antigen presentation) and adaptative immunity (T and B lymphocyte function). The maintenance of normal hair is dependant on the integrity of the dermis, epidermis and hair cycles. Beside its effect on epidermal differentiation, VDR plays a vital role in preserving the hair follicle integrity. While the relevance of VDR has been fully elucidated, the real value of vitamin D in the hair follicle cycle still remains uncertain. To date, results in literature remain contradicting and far from definitive; still, the role of vitamin D in the various forms of human alopecia is likely to be significant. The aim of this article is to review evidence about the role of vitamin D and its receptor in trichology, with a focus on scarring and non-scarring alopecia and in particular on the potential therapeutic use of Vitamin D for hair and scalp disorders.
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3.
Vitamin D Effects on the Immune System from Periconception through Pregnancy.
Schröder-Heurich, B, Springer, CJP, von Versen-Höynck, F
Nutrients. 2020;(5)
Abstract
Vitamin D is a well-known secosteroid and guardian of bone health and calcium homeostasis. Studies on its role in immunomodulatory functions have expanded its field in recent years. In addition to its impact on human physiology, vitamin D influences the differentiation and proliferation of immune system modulators, interleukin expression and antimicrobial responses. Furthermore, it has been shown that vitamin D is synthesized in female reproductive tissues and, by modulating the immune system, affects the periconception period and reproductive outcomes. B cells, T cells, macrophages and dendritic cells can all synthesize active vitamin D and are involved in processes which occur from fertilization, implantation and maintenance of pregnancy. Components of vitamin D synthesis are expressed in the ovary, decidua, endometrium and placenta. An inadequate vitamin D level has been associated with recurrent implantation failure and pregnancy loss and is associated with pregnancy-related disorders like preeclampsia. This paper reviews the most important data on immunomodulatory vitamin D effects in relation to the immune system from periconception to pregnancy and provides an insight into the possible consequences of vitamin D deficiency before and during pregnancy.
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4.
Effects of sunlight exposure and vitamin D supplementation on HIV patients.
Akimbekov, NS, Ortoski, RA, Razzaque, MS
The Journal of steroid biochemistry and molecular biology. 2020;:105664
Abstract
Unlike many vitamins derived predominantly from food sources, vitamin D is produced endogenously in the skin upon exposure to sunlight. Ethnicity, skin pigmentation, socioeconomic status, geographic location, climate and sunscreen; all of these factors contribute to the amount of insolation for any given individual. Insufficient insolation creates the prerequisites for vitamin D deficiency. This is particularly true in HIV-infected individuals, who are highly vulnerable to vitamin D insufficiency/deficiency, as it plays a huge role in the musculoskeletal and cardiovascular systems. Antiretroviral therapy may also be a factor in vitamin D deficiency. Today, as the issues of preventing common skeletal and non-skeletal diseases with HIV-infected people are becoming highly relevant, the maintenance of vitamin D levels through exposure to sunlight or supplementation appears to be an effective and safe solution. This review focuses on studies concerning the potential role of vitamin D supplementation through adequate sunlight exposure or dietary intake in HIV-infected people. The biology and epidemiology of HIV infection, as well as the issues related to vitamin D deficiency, its status on immune function, the effect of vitamin D against HIV disease progression and other health aspects of this vitamin, are briefly explained.
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5.
Exploring the Evidence for an Immunomodulatory Role of Vitamin D in Juvenile and Adult Rheumatic Disease.
Zou, J, Thornton, C, Chambers, ES, Rosser, EC, Ciurtin, C
Frontiers in immunology. 2020;:616483
Abstract
Vitamin D is synthesized in the skin following exposure to UVB radiation or is directly absorbed from the diet. Following hydroxylation in the liver and kidneys, vitamin D becomes its bioactive form, 1,25(OH)2D, which has been described to have potent immunomodulatory capacity. This review will focus on the effect of vitamin D in modulating the dysregulated immune system of autoimmune rheumatic diseases (ARD) patients across age, in particular in arthritis (rheumatoid arthritis and juvenile idiopathic arthritis), and systemic lupus erythematosus (with adult and juvenile onset). As well as delineating the impact of vitamin D on the innate and adaptive immune functions associated with each disease pathology, this review will also summarize and evaluate studies that link vitamin D status with disease prevalence, and supplementation studies that examine the potential benefits of vitamin D on disease outcomes. Exploring this evidence reveals that better designed randomized controlled studies are required to clarify the impact of vitamin D supplementation on ARD outcomes and general health. Considering the accessibility and affordability of vitamin D as a therapeutic option, there is a major unmet need for evidence-based treatment recommendations for the use of vitamin D in this patient population.
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6.
Possible Role of Vitamin D in Celiac Disease Onset.
Vici, G, Camilletti, D, Polzonetti, V
Nutrients. 2020;(4)
Abstract
Beside skeletal system maintenance and protection, possible extra-calcium roles of vitamin D have been recently described. In particular, studies have investigated possible roles of vitamin D as a key modulator of inflammation and immune mechanisms and of the intestinal mucosa barrier. In this regard, vitamin D has been considered as a factor that affects different conditions such as immune-mediated diseases. The new emerging role of vitamin D and its involvement in immune modulation has led it to be considered as a possible key factor involved in celiac disease (CD) onset. CD is a chronic immune-mediated enteropathy of the small intestine that is triggered by dietary gluten protein exposure in individuals who are genetically predisposed. However, along with gluten, other environmental factors are also involved in CD onset. The renewed interest in a molecule that offers great possibilities for new roles has led to an increase in studies, although there remains a lack of studies aimed at contextualizing the role of vitamin D on CD. This review aims to define the possible role of vitamin D in CD onset as it is presently understood, taking into account potential links among vitamin D, the immune system and CD.
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7.
Vitamin D Status Modulates Inflammatory Response in HIV+ Subjects: Evidence for Involvement of Autophagy and TG2 Expression in PBMC.
Currò, M, Visalli, G, Pellicanò, GF, Ferlazzo, N, Costanzo, MG, D'Andrea, F, Caccamo, D, Nunnari, G, Ientile, R
International journal of molecular sciences. 2020;(20)
Abstract
Conflicting results on the involvement of vitamin D deficiency in inflammatory and immune response in HIV+ subjects are reported. We aimed to characterize the possible influence of vitamin D status on changes in expression of tissue transglutaminase gene (TGM2) and other genes involved in inflammatory response and autophagy in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. HIV+ subjects (n = 57) under antiretroviral therapy (ART) and healthy controls (n = 40) were enrolled. mRNA levels of 1-alpha-hydroxylase (CYP27B1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), TGM2, microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related 5 homolog (ATG5), and Beclin 1 (BECN1) were quantified by real-time PCR. In HIV+ subjects, 25(OH)D3 plasma levels were negatively correlated with time since HIV diagnosis. In PBMC from HIV+ subjects, increases in gene expression of TNF-α and IFN-γ in comparison to controls were observed. The highest increase in TNF-α transcripts was observed in HIV+ subjects with deficient 25(OH)D3 levels. Autophagy-related genes LC3, ATG5, and BECN1 were down-regulated in HIV+ subjects. Moreover, TGM2 transcripts were up-regulated in PBMC from HIV+ subjects with 25(OH)D3 deficiency. Changes observed in PBMC from HIV+ subjects appeared to be dependent on vitamin D status. The present results suggest that vitamin D deficiency is associated with changes in the expression of markers of inflammation and autophagy, resulting in immune cell dysfunction.
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8.
Vitamin D status and the immune assessment in 22q11.2 deletion syndrome.
Legitimo, A, Bertini, V, Costagliola, G, Baroncelli, GI, Morganti, R, Valetto, A, Consolini, R
Clinical and experimental immunology. 2020;(3):272-286
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Abstract
22q11.2 deletion syndrome (22q11.2DS) is characterized by a heterogeneous phenotype, including alterations in phospho-calcium metabolism and immunodeficiency. We analyzed vitamin D status and the immune assessment, focusing on T cell subpopulations and dendritic cells (DCs) in a cohort of 17 pediatric 22q11.2DS patients and 17 age-matched healthy subjects. As antigen-presenting cells, DCs are the main target of vitamin D, promoting a tolerogenic T cell response. Patients were subdivided into three groups according to the parameters of phospho-calcium metabolism and serum levels of 25OHD: normal values, vitamin D deficiency and hypoparathyroidism. Different degrees of T cell deficiency, ranging from normal to partial T cell numbers, were observed in the cohort of patients. The group with vitamin D deficiency showed a significant reduction of naive T cells and a significant increase of central memory T cells compared to controls. In this group the number of circulating DCs was significantly reduced. DC decrease affected both myeloid and plasmacytoid DC subsets (mDCs and pDCs), with the most relevant reduction involving pDCs. A direct correlation between 25OHD levels and recent thymic emigrant (RTE) and DC number was identified. Despite the limited cohort analyzed, our results show that deficiency of the pDC subset in patients with 22q11.2DS may be included among the causative factors of the progressive increase of risk of autoimmune diseases in these patients. As most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, we suggest a potential role of vitamin D supplementation in preventing autoimmune or proinflammatory diseases in 22q11.2DS.
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9.
Association between vitamin D and endometriosis: a systematic review.
Kalaitzopoulos, DR, Lempesis, IG, Athanasaki, F, Schizas, D, Samartzis, EP, Kolibianakis, EM, Goulis, DG
Hormones (Athens, Greece). 2020;(2):109-121
Abstract
BACKGROUND Endometriosis is one of the most common gynecological diseases of reproductive age, with a prevalence of 5-10% and grave consequences for quality of life and fertility. Vitamin D (vit D), a classic regulator of plasma calcium concentration and skeleton mineralization, is also an effective modulator of the immune system. Several studies suggest that immunologic properties attributed to vit D along with vit D receptor (VDR) expression in reproductive tissues may be involved in the pathogenesis of endometriosis. OBJECTIVE To systematically review the literature for the association between components of vit D metabolism and endometriosis. MATERIALS AND METHODS A systematic review of the literature published in the Medline and Cochrane Central databases was conducted for original research articles on humans, published in any language. RESULTS Twenty-one studies were included in the systematic review. Among them, 12 examined the relationship of endometriosis with vit D metabolites, eight with vit D-binding protein (VDBP), three with VDR polymorphisms, and two with vit D regulatory enzymes. There are discrepancies between the outcomes of the available literature publications. CONCLUSIONS This is a systematic attempt to collect, evaluate, and present the known data on the association between vit D and endometriosis. Given the heterogeneity and the diversity of the present studies, more research is required to elucidate the association between vit D and endometriosis.
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10.
Paradoxical Response of Parathyroid Hormone to Vitamin D-Calcium Supplementation in Indian Children.
Mandlik, RM, Mughal, ZM, Khadilkar, AV, Ekbote, VH, Kajale, NA, Patwardhan, VG, Khadilkar, VV, Padidela, R
The Journal of pediatrics. 2020;:197-203
Abstract
OBJECTIVES To investigate the effect of oral vitamin D-calcium supplementation on serum intact parathyroid hormone (PTH), calcium, phosphorous, and alkaline phosphatase (ALK-P) concentrations in children with habitually low calcium intakes. STUDY DESIGN In this follow-up study to a randomized controlled trial that aimed to assess the effect of vitamin D-calcium supplementation on immunity, data related to dietary intake, anthropometry, and biochemistry [serum 25(OH)D and bone profile] were collected from 178 children-79 in the vitamin D group and 99 in the non-vitamin D group. RESULTS Dietary calcium to phosphorus intake ratio was 0.4:1. Baseline serum 25(OH)D concentration was 58.2 ± 10.9 nmol/L; 66% children were vitamin D sufficient and none deficient. After supplementation, vitamin D group, compared with the non-vitamin D group, had significantly (P < .05) greater 25(OH)D (83.9 ± 30.1 nmol/L vs 58.3 ± 15.7 nmol/L), significantly greater PTH (6.7 ± 3.6 pmol/L vs 5.5 ± 3.2 pmol/L), and positive correlation (rs = 0.24) between serum 25(OH)D and PTH (vs negative correlation [rs = -0.1] in non-vitamin D group). Mean concentrations of serum bone measures in the vitamin D group were calcium (2.2 ± 0.1 mmol/L), phosphorus (1.7 ± 0.2 mmol/L), and ALK-P (178.7 ± 40.7 IU/L). At follow-up, 1-year post-supplementation, in the vitamin D group, PTH concentrations continued to remain high (but not significantly different from levels at 6 months), with low normal serum calcium, high normal phosphate, and ALK-P in reference range. CONCLUSIONS In children who are vitamin D sufficient but with habitually low dietary calcium intake, vitamin D-calcium supplementation paradoxically and significantly increased serum PTH concentrations with no apparent effect on other bone biochemistry. Chronic low dietary calcium to phosphorus ratio is likely to have caused this paradoxical response.