1,25-Dihydroxyvitamin D
            <sub>3</sub>
            : a Novel Immunoregulatory Hormone

Tsoukas, Constantine D.; Provvedini, D; Manolagas, Stavros C.

doi:10.1126/science.6427926

Cited by 502 publications

(194 citation statements)

References 16 publications

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“…1,25(OH) 2 D 3 has also been demonstrated to stimulate T-suppressor-cell function, in vivo as well as in vitro (22,23), and is known to inhibit both T-and B-lymphocyte proliferation (24±26) as well as immunoglobulin production (25). 1,25(OH) 2 D 3 also inhibits the production of the growth-promoting lymphokine IL-2 (24,27,28), which was discovered to be the mechanism mediating the inhibition of lymphocyte proliferation (26,29). Activated T lymphocytes can serve as direct targets for 1,25(OH) 2 D 3 (30,31), but the effects of 1,25(OH) 2 D 3 on these cells are also the result of its actions on monocytes and macrophages in their role as APCs (32).…”

Section: Discussionmentioning

confidence: 99%

1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes

Canning

Grotenhuis

Wit

et al. 2001

European Journal of Endocrinology

215

142

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Objective: To study the effects of the active metabolite of vitamin D 3 , 1,25(OH) 2 D 3 , an immunomodulatory hormone, on the generation of so-called immature dendritic cells (iDCs) generated from monocytes (Mo-iDCs). Design and methods: Human peripheral blood monocytes were cultured to iDCs in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 for 1 week, with or without the extra addition of 10 28 M 1,25(OH) 2 D 3 to the culture. Their phenotypes (CD14, CD1a, CD83, HLA-DR, CD80, CD86 and CD40 expression) were examined by¯uorescence-activated cell sorting, and their T-cell stimulatory potential was investigated in allogeneic mixed lymphocyte reaction (allo-MLR). Additionally, their in vitro production of IL-10, IL-12 and transforming growth factor b (TGF-b) were examined by using the enzyme-linked immunosorbent assay. Results: When 1,25(OH) 2 D 3 was added to monocytes in culture with GM-CSF and IL-4, it hampered the maturation of Mo-iDCs. First, the phenotype of the 1,25(OH) 2 D 3 -differentiated DCs was affected, there being impaired downregulation of the monocytic marker CD14 and impaired upregulation of the markers CD1a, CD83, HLA-DR, CD80 and CD40. CD86 was expressed on more 1,25(OH) 2 D 3 -differentiated DCs. Secondly, the T-cell stimulatory capability of 1,25(OH) 2 D 3 -differentiated DCs was upregulated relative to the original monocytes to a lesser degree than DCs differentiated without 1,25(OH) 2 D 3 when tested in an allo-MLR. With regard to the production of cytokines, Staphylococcus aureus cowan 1 strain (SAC)-induced IL-10 production, although not enhanced, remained high in 1,25(OH) 2 D 3 -differentiated DCs, but was strongly downregulated in DCs generated in the absence of 1,25(OH) 2 D 3 . SAC/interferon-g-induced IL-12 production was clearly upregulated in both types of DC relative to those of the original monocytes, and TGF-b production was downregulated. Conclusion: Our data con®rm earlier reports showing that 1,25(OH) 2 D 3 hampers the maturation of fully active immunostimulatory major histocompatibility complex (MHC) class II+, CD1a+, CD80+ DCs from monocytes. Our data supplement the data from other reports by showing that the expression of CD86 was upregulated in 1,25(OH) 2 D 3 -differentiated DCs, whilst the capacity for IL-10 production remained high. Collectively, these data are in line with earlier descriptions of suppressive activities of this steroid-like hormone with respect to the stimulation of cell-mediated immunity.

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Section: Discussionmentioning

confidence: 99%

1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes

Canning

Grotenhuis

Wit

et al. 2001

European Journal of Endocrinology

215

142

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“…Vitamin D has potent immuno-modulator effects [40], affecting both innate, as evidenced by production of cathelicidin [41] , and adaptive immunity, through effects on T lymphocyte proliferation and function [42]. From animal studies, pre-treatment with 1,25OHD has been shown to prevent the development of both collagen and Lyme induced arthritis [14].…”

Section: Ai-associated Joint Pain and Vitamin D Status At 3 Monthsmentioning

confidence: 99%

Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study

Prieto-Alhambra

Javaid

Servitja

et al. 2010

Breast Cancer Res Treat

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Purpose: Aromatase inhibitor (AI) associated arthralgia limits adherence to therapy in breast cancer. The pathophysiology may involve vitamin D status. We wished to establish the optimal concentration of 25(OH)D that prevents or minimizes arthralgia. Methods:We used a prospective cohort of 290 women starting AI in whom baseline vitamin D was measured. All received daily vitamin D3 (800 IU) with calcium. Women with baseline 25(OH)D concentration <30 ng/ml also received 16,000 IU of D3 orally every two weeks. The primary outcome was incident or worsening joint pain derived from baseline and three month VAS for joint pain. Regression models were used to analyse the association between vitamin D concentrations at 3 months and pain adjusting for age, BMI, season when the sample was drawn, aromatase inhibitor (exemestane vs letrozole/anastrozole), prior tamoxifen therapy, baseline NTX, and previous fracture.Results: 90% of women had a 25(OH)D <30 ng/ml at baseline. After supplementation (daily 800 IU and additional additional 16,000 IU every two week), 50% of them still failed to reach adequate concentrations at three months. In the whole cohort, there was an increase in joint pain (mean 1.16 points SD 2.66; p<0.001) and the increase was significantly (p= 0.02) attenuated in those that reached concentrations of 25(OH)D of ≥40 ng/ml, with a lower risk of incident arthralgia (OR 0.12 ** [0.03 to 0.40]).Conclusion: A target concentration of 40ng/ml 25OHD may prevent development of AI arthralgia but higher loading doses are required to attain this level in women with deficiency at baseline.

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“…It has been demonstrated that pharmacological doses of the functional metabolite of vitamin D, 1␣,25-dihydroxyvitamin D 3 [1,25-(OH) 2 D 3 ], can greatly reduce or eliminate the incidence and progression of EAE in mice (12,13). In addition, 1,25-(OH) 2 D 3 has been shown to be an inhibitor of activated T cells both in vivo and in vitro and a modulator of antigen-presenting cells (14)(15)(16).…”

mentioning

confidence: 99%

CD8⁺T cells are not necessary for 1α,25-dihydroxyvitamin D₃to suppress experimental autoimmune encephalomyelitis in mice

Meehan

DeLuca

2002

Proc. Natl. Acad. Sci. U.S.A.

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In addition to its role in calcium and phosphorous homeostasis, 1␣,25-dihydroxyvitamin D3 [1,25-(OH)2D3] appears to be a modulator of the immune system. Administration of 1,25-(OH) 2D3 prevents disease in several autoimmune animal models, including experimental autoimmune encephalomyelitis (EAE). The vitamin D receptor is believed to mediate this activity. Among cells of the immune system, CD8 ؉ T cells have the highest levels of the vitamin D receptor. Because CD8 ؉ T cells have been implicated as both suppressors and effectors of the inflammation associated with multiple sclerosis and EAE, we examined the question of whether the 1,25-(OH) 2D3 suppression of EAE occurs through a CD8 ؉ T cell-dependent mechanism. To test this hypothesis, mice that are homozygous knockouts for the ␣ chain of the CD8 receptor and have been characterized as lacking functional CD8 ؉ T cells (CD8 ؉ ؊͞؊) were provided 1,25-(OH)2D3 in their diet before EAE induction. Although CD8 ؉ ؊͞؊ mice fed the same diet lacking 1,25-(OH) 2D3 have a high incidence of EAE, EAE did not occur in CD8 ؉ ؊͞؊ mice fed the diet containing 1,25-(OH)2D3. We conclude that CD8 ؉ T cells neither are needed nor do they play a role in the prevention of EAE by 1,25-(OH) 2D3.M ultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that is the leading cause of disease-associated neurological disability in western countries (1). This disease is characterized by destruction of the myelin sheaths that surround axons in the central nervous system and ultimately results in numerous neurological defects that manifest in symptoms including fatigue, limb spasticity, bladder dysfunction, and muscle weakness so severe that death is sometimes the result (2, 3). This inflammation is caused by either a breakdown in immunological self tolerance and͞or an infection that triggers central nervous system-specific T cells to form inflammatory lesions. Although very little is known about the triggering event for MS, it is clear that both environmental and genetic factors are involved (4). In examining environmental factors, the geographical distribution of MS must be considered. A north-to-south gradient of higher-to-lower MS incidence in the northern hemisphere has been demonstrated in epidemiology studies, whereas a similar gradient running south to north has been observed in the southern hemisphere (5, 6). In 1974, P. Goldberg noted that this MS incidence gradient correlated with the incidence of vitamin D deficiency in temperate regions, relative to equatorial regions (7). Further studies demonstrated a lower MS incidence in temperate areas where vitamin D is abundant because of increased sun exposure, high altitudes, or diets rich in fish oils (8)(9)(10)(11).Insights into the disease course of MS have been found by using the animal model experimental autoimmune encephalomyelitis (EAE). EAE is a CD4 ϩ T cell-mediated inflammatory demylenating disease that shares many similarities with MS and is induced by injecting an antigen such as myelin basic pro...

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1,25-Dihydroxyvitamin D ₃ : a Novel Immunoregulatory Hormone

Cited by 502 publications

References 16 publications

1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes

1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes

Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study

CD8⁺T cells are not necessary for 1α,25-dihydroxyvitamin D₃to suppress experimental autoimmune encephalomyelitis in mice

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1,25-Dihydroxyvitamin D 3 : a Novel Immunoregulatory Hormone

Cited by 502 publications

References 16 publications

1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes

1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes

Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study

CD8+T cells are not necessary for 1α,25-dihydroxyvitamin D3to suppress experimental autoimmune encephalomyelitis in mice

Contact Info

Product

Resources

About

1,25-Dihydroxyvitamin D ₃ : a Novel Immunoregulatory Hormone

CD8⁺T cells are not necessary for 1α,25-dihydroxyvitamin D₃to suppress experimental autoimmune encephalomyelitis in mice