Immunoregulation by 1,25-dihydroxyvitamin D3: Basic concepts

doi:10.1016/j.jsbmb.2005.06.002

The Journal of Steroid Biochemistry and Molecular Biology

Volume 97, Issues 1–2, October 2005, Pages 93-101

https://doi.org/10.1016/j.jsbmb.2005.06.002 Get rights and content

Abstract

1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃), the biologically active metabolite of Vitamin D₃, not only regulates bone and calcium metabolism but also exerts other biological activities, including immunomodulation via the nuclear Vitamin D receptor expressed in antigen-presenting cells and activated T cells. This regulation is mediated through interference with nuclear transcription factors such as NF-AT and NF-κB or by direct interaction with Vitamin D responsive elements in the promoter regions of cytokine genes. Dendritic cells (DCs) are primary targets for the immunomodulatory activity of 1,25(OH)₂D₃, as indicated by inhibited DC differentiation and maturation, leading to down-regulated expression of MHC-II, costimulatory molecules and IL-12. Moreover, 1,25(OH)₂D₃ enhances IL-10 production and promotes DC apoptosis. Together, these effects of 1,25(OH)₂D₃ inhibit DC-dependent T cell activation. Immunomodulation by 1,25(OH)₂D₃ and its analogs in vivo has been demonstrated in different models of autoimmune diseases and transplantation. Moreover, combining analogs with other immunosuppressants leads to synergism in models of autoimmunity and transplantation. The availability of 1,25(OH)₂D₃ analogs with immunomodulatory activity at non-hypercalcemic doses may allow exploitation of their immunomodulatory effects in a clinical setting of treatment of autoimmune diseases and prevention of allograft rejection.

Section snippets

Introduction: 1,25-dihydroxyvitamin D₃

1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃), originally described as an essential hormone for bone and mineral homeostasis, is the biologically active form of the secosteroid Vitamin D₃. Although Vitamin D₃ can be derived from nutrition (with as major dietary sources fortified dairy products, fatty fish and fish liver oils), the main supply of Vitamin D₃ is obtained through photosynthesis in the skin. Exposure of skin to ultraviolet (UV) light (270–300 nm) catalyzes the first step in the Vitamin D₃

1,25(OH)₂D₃ and the immune system: receptors and metabolism

The discovery that the VDR is constitutively expressed by antigen-presenting cells (APCs) such as macrophages and dendritic cells (DCs) and inducibly expressed by lymphocytes following activation suggests a role for 1,25(OH)₂D₃ in the immune system [5]. Moreover, the enzyme responsible for the final and rate limiting hydroxylation step in the synthesis of 1,25(OH)₂D₃, 25(OH)D₃-1-α-hydroxylase, is expressed by activated macrophages [6] making them able to synthesize and secrete 1,25(OH)₂D₃ in a

T lymphocytes

After the discovery of VDR expression in most cells of the immune system, a direct effect of 1,25(OH)₂D₃ on T lymphocytes was shown. Antigen- or lectin-stimulated human and murine T lymphocyte proliferation, cytokine secretion and cell cycle progression from G_1a to G_1b are inhibited by in vitro addition of 1,25(OH)₂D₃. The transcription of several key cytokines of T helper (Th)1 lymphocytes, such as IFN-γ and interleukin (IL)-2, is a direct target of 1,25(OH)₂D₃. By inhibiting IFN-γ

Molecular pathways of 1,25(OH)₂D₃-mediated immune regulation

Next to the classical mechanism of action of 1,25(OH)₂D₃, through binding of the ligand-activated transcription factor VDR to VDREs within the promoter region of 1,25(OH)₂D₃-responsive genes and thus eventually regulating the transcription rate of these genes, there is abundant evidence that the regulation of the transcription of many cytokine genes by 1,25(OH)₂D₃ results indirectly from modulation of other intracellular signaling pathways. In activated T lymphocytes 1,25(OH)₂D₃-mediated

In vivo immunomodulatory potential of 1,25(OH)₂D₃ and its analogs

The fact that 1,25(OH)₂D₃ influences the immune system, not merely by suppression, but by immune modulation through induction of immune shifts and regulator cells, makes this compound very appealing for clinical use, especially in the treatment and prevention of autoimmune diseases and in the prevention of graft rejection. The major drawback in the widespread clinical application of 1,25(OH)₂D₃ for its immunomodulatory effects, are the dose-limiting side effects including hypercalcemia,

Effects of Vitamin D deficiency on the immune system

Next to the pharmacological effects of 1,25(OH)₂D₃ in the immune system, several data point towards a possible physiological immune function of 1,25(OH)₂D₃, suggesting that Vitamin D deficiency could lead to immune malfunctioning. Subjects with severe Vitamin D deficiency are abnormally susceptible to infections such as tuberculosis [55]. Different studies provide evidence for defects in macrophage functions, such as chemotaxis, phagocytosis and the production of proinflammatory cytokines, in

Conclusions

The widespread presence of VDR in the immune system and the regulated expression of 1-α-hydroxylase by specific immune signals suggest a paracrine immunomodulatory role for 1,25(OH)₂D₃. Indeed, 1,25(OH)₂D₃ has pleiotropic activities in the immune system (summarized in Fig. 1). Strikingly, 1,25(OH)₂D₃ uses several different molecular mechanisms to regulate cytokine expression, either directly targeting transcription initiation and regulation or indirectly interfering with other intracellular

Acknowledgements

The authors would like to thank the Belgian federal government, the Katholieke Universiteit Leuven (KUL), the European Community (EU), the Juvenile Diabetes Research Foundation (JDRF) and the Flemish Research Foundation (FWO) for support.

References (64)

C. Mathieu et al.
The coming of age of 1,25-dihydroxyvitamin D₃ analogs as immunomodulatory agents
Trends Mol. Med.
(2002)
K.S. Chen et al.
Cloning of the human 1 alpha,25-dihydroxyvitamin D₃ 24-hydroxylase gene promoter and identification of two Vitamin D-responsive elements
Biochim. Biophys. Acta
(1995)
R. Koren et al.
1,25-Dihydroxyvitamin D₃ enhances prostaglandin E2 production by monocytes. A mechanism which partially accounts for the antiproliferative effect of 1,25(OH)₂D₃ on lymphocytes
FEBS Lett.
(1986)
L. Giovannini et al.
1,25-dihydroxyvitamin D₃ dose-dependently inhibits LPS-induced cytokines production in PBMC modulating intracellular calcium
Transplant. Proc.
(2001)
A.G. van Halteren et al.
1alpha,25-dihydroxyvitamin D₃ or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis
J. Autoimmun.
(2004)
M.T. Cantorna et al.
1125-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease
J. Nutr.
(2000)
C.A. Redaelli et al.
1-alpha,25-Dihydroxycholecalciferol reduces rejection and improves survival in rat liver allografts
Hepatology
(2001)
D.L. Bertolini et al.
Immunomodulatory effects of Vitamin D analog KH1060 on an experimental skin transplantation model
Transplant. Proc.
(1999)
C.A. Redaelli et al.
1alpha,25-dihydroxyvitamin D₃ shows strong and additive immunomodulatory effects with cyclosporine A in rat renal allotransplants
Kidney Int.
(2002)
D.D. Branisteanu et al.
Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1-alpha,25-(OH)₂D₃
J. Neuroimmunol.
(1995)

D.D. Branisteanu et al.

Synergism between sirolimus and 1,25-dihydroxyvitamin D₃ in vitro and in vivo

J. Neuroimmunol.

(1997)

A.A. Licata

Bisphosphonate therapy

Am. J. Med. Sci.

(1997)

E. Van Etten et al.

Combination of a 1,25-dihydroxyvitamin D₃ analog and a bisphosphonate prevents experimental autoimmune encephalomyelitis and preserves bone

Bone

(2003)

S. Yang et al.

Vitamin D deficiency suppresses cell-mediated immunity in vivo

Arch. Biochem. Biophys.

(1993)

E. Hypponen et al.

Intake of Vitamin D and risk of type 1 diabetes: a birth-cohort study

Lancet

(2001)

C. Mathieu et al.

Seasonality of birth in patients with type 1 diabetes

Lancet

(2002)

G. Jones et al.

Current understanding of the molecular actions of Vitamin D

Physiol. Rev.

(1998)

M.R. Haussler et al.

The nuclear Vitamin D receptor: biological and molecular regulatory properties revealed

J. Bone Miner. Res.

(1998)

C. Carlberg et al.

Gene regulation by Vitamin D₃

Crit. Rev. Eukaryot. Gene Expr.

(1998)

E. Marcinkowska

A run for a membrane Vitamin D receptor

Biol. Signals Recept.

(2001)

L. Overbergh et al.

Identification and immune regulation of 25-hydroxyvitamin D-1-alpha-hydroxylase in murine macrophages

Clin. Exp. Immunol.

(2000)

M. Hewison et al.

Differential regulation of Vitamin D receptor and its ligand in human monocyte-derived dendritic cells

J. Immunol.

(2003)

M. Vidal et al.

Stat1-Vitamin D receptor interactions antagonize 1,25-dihydroxyvitamin D transcriptional activity and enhance stat1-mediated transcription

Mol. Cell Biol.

(2002)

M. Cippitelli et al.

Vitamin D₃: a transcriptional modulator of the interferon-gamma gene

Eur. J. Immunol.

(1998)

A. Takeuchi et al.

Nuclear factor of activated T cells (NFAT) as a molecular target for 1alpha,25-dihydroxyvitamin D₃-mediated effects

J. Immunol.

(1998)

A. Boonstra et al.

1alpha,25-Dihydroxyvitamin D₃ has a direct effect on naive CD4⁺ T cells to enhance the development of Th2 cells

J. Immunol.

(2001)

L. Overbergh et al.

1alpha,25-dihydroxyvitamin D₃ induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p524-543)

Diabetes

(2000)

A. Tobler et al.

Granulocyte-macrophage colony-stimulating factor. Sensitive and receptor-mediated regulation by 1,25-dihydroxyvitamin D₃ in normal human peripheral blood lymphocytes

J. Clin. Invest.

(1987)

M. Cippitelli et al.

Negative regulation of CD95 ligand gene expression by Vitamin D₃ in T lymphocytes

J. Immunol.

(2002)

H. Xu et al.

1,25-Dihydroxyvitamin D₃ exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes

Scand. J. Immunol.

(1993)

G. Penna et al.

1 Alpha,25-dihydroxyvitamin D₃ inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation

J. Immunol.

(2000)

A.G. van Halteren et al.

Redirection of human autoreactive T-cells Upon interaction with dendritic cells modulated by TX527, an analog of 1,25 dihydroxyvitamin D₃

Diabetes

(2002)

Cited by (738)

Molecular effects of Vitamin-D and PUFAs metabolism in skeletal muscle combating Type-II diabetes mellitus
2024, Gene
Multiple post-receptor intracellular alterations such as impaired glucose transfer, glucose phosphorylation, decreased glucose oxidation, and glycogen production contribute to insulin resistance (IR) in skeletal muscle, manifested by diminished insulin-stimulated glucose uptake. Type-2 diabetes mellites (T2DM) has caused by IR, which is also seen in obese patients and those with metabolic syndrome. The Vitamin-D receptor (VDR) and poly unsaturated fatty acids (PUFAs) roles in skeletal muscle growth, shapes, and function for combating type-2 diabetes have been clarified throughout this research. VDR and PUFAs appears to show a variety of effects on skeletal muscle, in addition it shows a promising role on bone and mineral homeostasis. Individuals having T2DM are reported to suffer from severe muscular weakness and alterations in shape of the muscle. Several studies have investigated the effect on VDR on muscular strength and mass, which leads to Vitamin-D deficiency (VDD) in individuals, in which most commonly seen in elderly. VDR has been shown to affect skeletal cellular proliferation, intracellular calcium handling, as well as genomic activity in a variety of different ways such as muscle metabolism, insulin sensitivity, which is the major characteristic pathogenesis for IR in combating T2DM. The identified VDR gene polymorphisms are ApaI, TaqI, FokI, and BsmI that are associated with T2DM. This review collates informations on the mechanisms by which VDR activation takes place in skeletal muscles. Despite the significant breakthroughs made in recent decades, various studies show that IR affects VDR and PUFAs metabolism in skeletal muscle. Therefore, this review collates the data to show the role of VDR and PUFAs in the skeletal muscles to combat T2DM.
The role of micronutrients on the treatment of diabetes
2024, Human Nutrition and Metabolism
In the last two decades, there has been a significant increase in the number of individuals worldwide who are affected by diabetes. This review article aims to explore the correlation between specific vitamins and diabetes. It has been observed that individuals with diabetes tend to have lower levels of certain antioxidant vitamins, namely A, C, and E. This decrease in vitamin levels is believed to be a consequence of the need to manage oxidative stress caused by issues with glucose metabolism. Additionally, retinol-binding protein plays a role in regulation and adipocytokine function. Diabetics also exhibit reduced levels of thiamine, pyridoxine, and biotin. Research has indicated that diabetes can hinder the absorption of various nutrients, including vitamins B9 and B12, necessitating frequent replenishment of these vitamins. Insufficient levels of vitamin D have been linked to an increased risk of developing diabetes and related complications such as cardiovascular disease. While some studies suggest that vitamin K supplementation may improve glucose metabolism, it remains uncertain whether it can prevent or repair oxidative damage. Excessive vitamin supplementation has been shown to have negative effects, as demonstrated by numerous studies. The review that follows will analyze the association between several nutrients, specifically vitamins A, D, C, B3, B6, B9, Zn, B12, E, B1/K, and iron, and the pathways implicated in diabetes, as well as their potential regulatory effects.
Impact of micronutrients and nutraceuticals on cognitive function and performance in Alzheimer's disease
2024, Ageing Research Reviews
Alzheimer's disease (AD) is a major global health problem today and is the most common form of dementia. AD is characterized by the formation of β-amyloid (Aβ) plaques and neurofibrillary clusters, leading to decreased brain acetylcholine levels in the brain. Another mechanism underlying the pathogenesis of AD is the abnormal phosphorylation of tau protein that accumulates at the level of neurofibrillary aggregates, and the areas most affected by this pathological process are usually the cholinergic neurons in cortical, subcortical, and hippocampal areas. These effects result in decreased cognitive function, brain atrophy, and neuronal death. Malnutrition and weight loss are the most frequent manifestations of AD, and these are also associated with greater cognitive decline. Several studies have confirmed that a balanced low-calorie diet and proper nutritional intake may be considered important factors in counteracting or slowing the progression of AD, whereas a high-fat or hypercholesterolemic diet predisposes to an increased risk of developing AD. Especially, fruits, vegetables, antioxidants, vitamins, polyunsaturated fatty acids, and micronutrients supplementation exert positive effects on aging-related changes in the brain due to their antioxidant, anti-inflammatory, and radical scavenging properties. The purpose of this review is to summarize some possible nutritional factors that may contribute to the progression or prevention of AD, understand the role that nutrition plays in the formation of Aβ plaques typical of this neurodegenerative disease, to identify some potential therapeutic strategies that may involve some natural compounds, in delaying the progression of the disease.
Transcriptome analysis of T cells from Ldlr<sup>−/−</sup> mice and effects of in vitro vitamin D treatment
2024, Journal of Nutritional Biochemistry
Vitamin D is known for its immunosuppressive effects on T cells, suppressing Th1 and Th17 and promoting Treg differentiation. Th1 cells contribute to inflammatory responses such as inflammatory cytokine production and macrophage activation, which accelerate the progression of atherosclerosis. However, the mechanisms underlying the modulation of T cell functions by vitamin D in atherosclerosis have not been investigated. This study analyzed the gene expression profiles of T cells, using RNA-seq transcriptome analysis, to investigate the effects of in vitro vitamin D treatment on T cell differentiation and signal transduction pathways in Ldlr knock-out (Ldlr^−/−) mice. C57BL/6 mice were randomly assigned to two groups and fed a control diet (CON) or a Western diet (WD) for 16 weeks, while Ldlr^−/- mice (LDLR^−/−) were fed a Western diet. Splenic T cells were isolated and stimulated with anti-CD3e and anti-CD28 mAb for 48 h with or without 10 nM 1,25(OH)₂D₃. RNA sequencing was performed, followed by KEGG and GO enrichment analyses. Populations of T cell subsets and cytokine production were measured to assess T cell lineage differentiation. The JAK-STAT, HIF-1, and calcium signaling pathways of Ldlr^−/− mice significantly differed from those of control mice, and 1,25(OH)₂D₃ treatment affected MAPKKK binding molecular function of Ldlr^−/− mice. Percentages of Th1 cells and IL-17 production were significantly reduced by 1,25(OH)₂D₃ treatment in all three mouse groups. These results suggest that 1,25(OH)₂D₃ has anti-inflammatory effects in atherosclerosis and is involved in cell signaling pathways that could prevent disease progression by regulating T cell differentiation and effector functions.
Vitamin D3 supplementation could ameliorate the inflammatory and redox status in the muscular phase of trichinellosis
2023, Parasitology International
Nutritional supplements, particularly vitamin D, have been widely used worldwide in the treatment of various infections, including parasites. This study aimed to evaluate the potential effects of vitamin D3 supplementation on the muscular phase of trichinellosis in experimental animals. Mice were divided as follows: (group I): infected untreated, (group IIa) infected and treated with vitamin D3 for 12 doses beginning 2 weeks before infection and continuing after infection, (group IIb) infected and treated with vitamin D3 for 8 doses beginning on the same day of infection, (group III) normal control, (group IVa) which received vitamin D3 for 12 doses and (group IVb) which received vitamin D3 for 8 doses. Mice were sacrificed 35 days after infection and total muscle larval count, and histopathological examination of muscle samples with immunohistochemical staining of cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) were performed. Muscle relative cathelicidin mRNA expression was assessed, as well as serum levels of muscle enzymes CK and LDH, interleukin-4 (IL-4), IL-10, IL-17 and interferon-gamma (INF-γ). Vitamin D3 supplementation significantly reduced muscle larval count, inflammatory cellular infiltration, COX2 and iNOS expression. Furthermore, it increased cathelicidin gene expression, decreased serum levels of CK and LDH and affected serum cytokine levels, increasing serum IL-4 and IL10 levels while decreasing serum INF γ and IL-17. In conclusion, vitamin D3 supplementation has favorable outcomes on the muscle phase of trichinellosis, including anti-inflammatory, antioxidant, and immunomodulatory effects.
Vitamin D and SARS-CoV-2 Infection: SERVE Study (SARS-CoV-2 Exposure and the Role of Vitamin D among Hospital Employees)
2023, Journal of Nutrition
Recognition of the role of vitamin D in immune function has led to interest in its relationship with SARS-CoV-2 infection. Although clinical studies to date have had conflicting results, many individuals currently take high doses of vitamin D to prevent infection.
The goal of this study was to investigate the relationship between serum 25-hydroxyvitamin D (25OHD) and vitamin D supplement use with incident SARS-CoV-2 infection.
In this prospective cohort study, 250 health care workers were enrolled at a single institution and observed for 15 mo. Participants completed questionnaires every 3 mo regarding new SARS-CoV-2 infection, vaccination, and supplement use. Serum was drawn at baseline, 6, and 12 mo for 25OHD and SARS-CoV-2 nucleocapsid antibodies.
The mean age of the participants was 40 y, BMI 26 kg/m², 71% were Caucasian, and 78% female. Over 15 mo, 56 participants (22%) developed incident SARS-CoV-2 infections. At baseline, ∼50% reported using vitamin D supplements (mean daily dose 2250 units). Mean serum 25OHD was 38 ng/mL. Baseline 25OHD did not predict incident SARS-CoV-2 infection (OR: 0.98; 95% CI: 0.80, 1.20). Neither the use of vitamin D supplements (OR: 1.18; 95% CI: 0.65, 2.14) or supplement dose was associated with incident infection (OR: 1.01 per 100-units increase; 95% CI: 0.99, 1.02).
In this prospective study of health care workers, neither serum 25OHD nor the use of vitamin D supplements was associated with the incident SARS-CoV-2 infection. Our findings argue against the common practice of consuming high-dose vitamin D supplements for the presumed prevention of COVID-19.

View all citing articles on Scopus

View full text

Immunoregulation by 1,25-dihydroxyvitamin D3: Basic concepts

Abstract

Section snippets

Introduction: 1,25-dihydroxyvitamin D3

1,25(OH)2D3 and the immune system: receptors and metabolism

T lymphocytes

Molecular pathways of 1,25(OH)2D3-mediated immune regulation

In vivo immunomodulatory potential of 1,25(OH)2D3 and its analogs

Effects of Vitamin D deficiency on the immune system

Conclusions

Acknowledgements

Trends Mol. Med.

Biochim. Biophys. Acta

FEBS Lett.

Transplant. Proc.

J. Autoimmun.

J. Nutr.

Hepatology

Transplant. Proc.

Kidney Int.

J. Neuroimmunol.

J. Neuroimmunol.

Am. J. Med. Sci.

Bone

Arch. Biochem. Biophys.

Lancet

Lancet

Current understanding of the molecular actions of Vitamin D

Physiol. Rev.

The nuclear Vitamin D receptor: biological and molecular regulatory properties revealed

J. Bone Miner. Res.

Gene regulation by Vitamin D3

Crit. Rev. Eukaryot. Gene Expr.

A run for a membrane Vitamin D receptor

Biol. Signals Recept.

Identification and immune regulation of 25-hydroxyvitamin D-1-alpha-hydroxylase in murine macrophages

Clin. Exp. Immunol.

Differential regulation of Vitamin D receptor and its ligand in human monocyte-derived dendritic cells

J. Immunol.

Stat1-Vitamin D receptor interactions antagonize 1,25-dihydroxyvitamin D transcriptional activity and enhance stat1-mediated transcription

Mol. Cell Biol.

Vitamin D3: a transcriptional modulator of the interferon-gamma gene

Eur. J. Immunol.

Nuclear factor of activated T cells (NFAT) as a molecular target for 1alpha,25-dihydroxyvitamin D3-mediated effects

J. Immunol.

1alpha,25-Dihydroxyvitamin D3 has a direct effect on naive CD4+ T cells to enhance the development of Th2 cells

J. Immunol.

1alpha,25-dihydroxyvitamin D3 induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p524-543)

Diabetes

Granulocyte-macrophage colony-stimulating factor. Sensitive and receptor-mediated regulation by 1,25-dihydroxyvitamin D3 in normal human peripheral blood lymphocytes

J. Clin. Invest.

Negative regulation of CD95 ligand gene expression by Vitamin D3 in T lymphocytes

J. Immunol.

1,25-Dihydroxyvitamin D3 exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes

Scand. J. Immunol.

1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation

J. Immunol.

Redirection of human autoreactive T-cells Upon interaction with dendritic cells modulated by TX527, an analog of 1,25 dihydroxyvitamin D3

Diabetes

Immunoregulation by 1,25-dihydroxyvitamin D₃: Basic concepts

Introduction: 1,25-dihydroxyvitamin D₃

1,25(OH)₂D₃ and the immune system: receptors and metabolism

Molecular pathways of 1,25(OH)₂D₃-mediated immune regulation

In vivo immunomodulatory potential of 1,25(OH)₂D₃ and its analogs

Gene regulation by Vitamin D₃

Vitamin D₃: a transcriptional modulator of the interferon-gamma gene

Nuclear factor of activated T cells (NFAT) as a molecular target for 1alpha,25-dihydroxyvitamin D₃-mediated effects

1alpha,25-Dihydroxyvitamin D₃ has a direct effect on naive CD4⁺ T cells to enhance the development of Th2 cells

1alpha,25-dihydroxyvitamin D₃ induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p524-543)

Granulocyte-macrophage colony-stimulating factor. Sensitive and receptor-mediated regulation by 1,25-dihydroxyvitamin D₃ in normal human peripheral blood lymphocytes

Negative regulation of CD95 ligand gene expression by Vitamin D₃ in T lymphocytes

1,25-Dihydroxyvitamin D₃ exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes

1 Alpha,25-dihydroxyvitamin D₃ inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation

Redirection of human autoreactive T-cells Upon interaction with dendritic cells modulated by TX527, an analog of 1,25 dihydroxyvitamin D₃