The role of vitamin D in autoimmune diseases: could sex make the difference?

AbstractOver the last decades, a central role for vitamin D in immune modulation has been well established. The active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with vitamin D receptor, exerts different activities on the innate and adaptive immune system, among which suppression of inflammation and promotion of tolerogenic responses. Vitamin D insufficiency has been linked to autoimmune disorders that commonly display significant differences between females and males due to genetic, epigenetic, hormonal, and environmental factors. Notably, a number of studies recently showed a cross-talk between vitamin D and the sex hormone estrogen. Estrogen-mediated effects on immune response may favor a Th1 profile or a Th2 profile, depending on hormone concentration. Thus, estrogen-mediated effects appear to be variable on autoimmunity depending on its concentration but also on the pathogenic mechanisms underlying the different autoimmune diseases (i.e., Th1- or Th2-mediated diseases). Notably, estrogen has been demonstrated to enhance vitamin D function favoring its accumulation, and increasing the expression of vitamin D receptor, thus resulting in a more potent anti-inflammatory response in females than males. On the other hand, vitamin D has been shown to downregulate in immune cells the expression of aromatase, which converts testosterone to estrogen, leading to a decrease in estrogen level. Overall, available data allow us to hypothesize a higher protective effect of vitamin D-based therapeutic approaches in women, at least in fertile age, than in men. Future studies are needed to expand current knowledge on the immunomodulatory role of vitamin D in a sex and gender perspective, paving the way to a more personalized therapeutic approach in autoimmune diseases.

Download Full-text

The Role of Vitamin D and Vitamin D Receptor in Immunity toLeishmania majorInfection

Journal of Parasitology Research ◽

10.1155/2012/134645 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 18

Author(s):

James P. Whitcomb ◽

Mary DeAgostino ◽

Mark Ballentine ◽

Jun Fu ◽

Martin Tenniswood ◽

...

Keyword(s):

Vitamin D ◽

Immune Responses ◽

Vitamin D Receptor ◽

Leishmania Major ◽

Active Form ◽

Wild Type ◽

Vitamin D Signaling ◽

Deficient Mice ◽

Th 1

Vitamin D signaling modulates a variety of immune responses. Here, we assessed the role of vitamin D in immunity to experimental leishmaniasis infection in vitamin D receptor-deficient mice (VDRKO). We observed that VDRKO mice on a genetically resistant background have decreasedLeishmania major-induced lesion development compared to wild-type (WT) mice; additionally, parasite loads in infected dermis were significantly lower at the height of infection. Enzymatic depletion of the active form of vitamin D mimics the ablation of VDR resulting in an increased resistance toL. major. Conversely, VDRKO or vitamin D-deficient mice on the susceptible Th2-biased background had no change in susceptibility. These studies indicate vitamin D deficiency, either through the ablation of VDR or elimination of its ligand, 1,25D3, leads to an increase resistance toL. majorinfection but only in a host that is predisposed for Th-1 immune responses.

Download Full-text

The Emerging Role of Vitamin D and Vitamin D Receptor in Diabetic Nephropathy

BioMed Research International ◽

10.1155/2020/4137268 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Min Lei ◽

Zhangsuo Liu ◽

Jia Guo

Keyword(s):

Vitamin D ◽

Diabetic Nephropathy ◽

Signaling Pathway ◽

Vitamin D Receptor ◽

Interstitial Fibrosis ◽

Microvascular Complications ◽

Active Form ◽

Nuclear Hormone Receptor ◽

Protective Effects

Diabetic nephropathy (DN), one of the most common and severe microvascular complications of diabetes mellitus (DM), is an important risk factor for DM patient’s death. Nowadays, DN has become the leading cause of end-stage renal disease (ESRD) in most countries without effective therapeutic methods. Recently, the renoprotective effects mediated by vitamin D (VD) and vitamin D receptor (VDR) have been evidenced. VD, a kind of steroid with the active form 1,25(OH)2D3, has been known for the crucial roles in the modulation of serum calcium and phosphorus concentrations. It exerts important functions by binding with its receptor VDR.VDR, a transcription factor located at chromosome 12 containing 9 exons, is one of the nonsteroid nuclear hormone receptor superfamily, which participates in transcriptional regulation of genes in tissue- and cell-specific ways. Increasing evidences have demonstrated that VD/VDR signaling pathway possesses a variety of kidney-protective effects in DN patients, such as antiproteinuria, antifibrosis, anti-inflammatory, and preventing podocyte damage. Although there are many studies on the role of the VD/VDR signaling pathway in DN, the effects and mechanisms still need to be further explained. This review summarized the multiple roles of VD/VDR in podocyte injury, tubule lesions, interstitial fibrosis, and inflammation, as well as the clinical applications about DN to explore much more and effective therapeutic methods for DN.

Download Full-text

Faculty Opinions recommendation of Renoprotective role of the vitamin D receptor in diabetic nephropathy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1097755.553873 ◽

2008 ◽

Author(s):

Craig Langman

Keyword(s):

Vitamin D ◽

Diabetic Nephropathy ◽

Vitamin D Receptor

Download Full-text

Role of genetic variants of Vitamin D receptor, Toll-like receptor 2 and Toll-like receptor 4 in extrapulmonary tuberculosis

Microbial Pathogenesis ◽

10.1016/j.micpath.2021.104911 ◽

2021 ◽

pp. 104911

Author(s):

Bilal Ahmad Wani ◽

Faheem Shehjar ◽

Sonaullah Shah ◽

Ajaz Koul ◽

Adfar Yusuf ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Genetic Variants ◽

Extrapulmonary Tuberculosis ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Toll Like Receptor 2

Download Full-text

Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

Endocrine Reviews ◽

10.1210/er.2016-1070 ◽

2016 ◽

Vol 37 (5) ◽

pp. 521-547 ◽

Cited By ~ 97

Author(s):

Peter J. Tebben ◽

Ravinder J. Singh ◽

Rajiv Kumar

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Active Form ◽

Elevated Serum ◽

Diagnosis And Treatment ◽

Vitamin D Metabolites ◽

Hydroxyvitamin D ◽

Dihydroxyvitamin D ◽

Stone Formers ◽

25 Hydroxyvitamin D

AbstractHypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.

Download Full-text

Role of Rb Family in Vitamin D Receptor-Mediated Anti-Tumor Effects in Ovarian Cancer Cells.

10.1210/endo-meetings.2010.part1.p1.p1-9 ◽

2010 ◽

pp. P1-9-P1-9

Author(s):

J Tang ◽

P Li ◽

AKW Tse ◽

SV Nicosia ◽

X Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Vitamin D ◽

Cancer Cells ◽

Vitamin D Receptor ◽

Ovarian Cancer Cells

Download Full-text

Associations between Vitamin D and Type 2 Diabetes Mellitus: The Role of Vitamin D Receptor and Binding Protein

Journal of Diabetes Mellitus ◽

10.4236/jdm.2020.104018 ◽

2020 ◽

Vol 10 (04) ◽

pp. 222-235

Author(s):

Eman S. Arafat ◽

Inass M. Taha ◽

Shahad W. Kattan ◽

Nouf Abubakr Babteen ◽

Iman Fawzy

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Vitamin D ◽

Type 2 Diabetes Mellitus ◽

Vitamin D Receptor ◽

Binding Protein

Download Full-text

POTENTIAL ROLE OF VITAMIN D RECEPTOR AGONIST IN ACETAMINOPHEN-INDUCED HEPATIC INJURY: ROLE OF CASPASE-1

Ain Shams Medical Journal ◽

10.21608/asmj.2021.192511 ◽

2021 ◽

Vol 72 (2) ◽

pp. 251-265

Author(s):

Atef Abood ◽

Hosam Eldin Awad ◽

Sherif Hassan

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Receptor Agonist ◽

Hepatic Injury ◽

Potential Role ◽

Caspase 1

Download Full-text

Assessment of vitamin D among Sudanese Patients with Hypothyroidism

10.30574/ijbpsa.2021.1.2.0024 ◽

2021 ◽

Vol 1 (2) ◽

pp. 057-061

Author(s):

Hasna Osman Fadalla Mohamed ◽

Omer Fadol Edris ◽

Gad Allah Modawe ◽

Suhair Abdelrahman Ahmed

Keyword(s):

Vitamin D ◽

Autoimmune Diseases ◽

Vitamin D Deficiency ◽

Vitamin D Supplementation ◽

Control Hospital ◽

Study Population ◽

Thyroid Profile ◽

Methods Analytical ◽

The Relationship

Background: Vitamin D deficiency is a worldwide health issue and its role as an immune modulator has recently been emphasized. Evidence increasingly indicates the important role of vitamin D in reducing the incidence of autoimmune diseases. However, at this time the search for its role in autoimmune diseases and thyroid is not critical. Objectives: The study aimed to assess the relationship between vitamin D deficiency in Sudanese patients with hypothyroidism. Methods: Analytical case control hospital based study, conducted in Fadil Hospital and Police Hospital, Khartoum city, Khartoum state. The study carried out from March 2018 to September 2018. A total of 100 subjects were enrolled in the study. Vitamin D deficiency was set at levels below 20 ng / ml. Thyroid hormones (TSH, T3 and T4) were assessed in all participants using auto analyzer TOSOH AIA 313,while vitamin D was estimated using ELIZA. The data were analyzed using SPSS version (21). Results: The study included 76(76%) females and 24(24%) males, no significance differences between thyroid profile among study population.75 (75%) deficiency of vitamin D and 25(25%) normal vitamin D. vitamin D deficiency was significantly lower in female than male with( p =0.001). Conclusion: The results indicated that patients with hypothyroidism suffer from vitamin D deficiency significantly associated with the degree and severity of hypothyroidism. This encourages the desirability of vitamin D supplementation and recommends the detection of vitamin D deficiency for all hypothyroidism patients.

Download Full-text