Distinct Target Cells and Effects of lα,25-Dihydroxyvitamin D<sub>3</sub>and Glucocorticoids in the Rat Thymus Gland*

Provvedini, D; Y, Sakagami; Manolagas, Stavros C.

doi:10.1210/endo-124-3-1532

Cited by 16 publications

(4 citation statements)

References 26 publications

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“…Medullary thymocytes also express the vitamin D receptor and vitamin D signaling inhibits mitogenic stimulation of these cells (53, 55) which may negatively impact upon peripheral T-lineage reconstitution. We observed a reduction of regulatory T cells (Tregs) in the thymus and in the periphery of 8-week-old Kl/Kl mice (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Thymic Epithelial Cell Support of Thymopoiesis Does Not Require Klotho

Xing

Smith

Goetz

et al. 2018

The Journal of Immunology

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Age-related thymic involution is characterized by a decrease in thymic epithelial cell (TEC) number and function parallel to a disruption in their spatial organization, resulting in defective thymocyte development and proliferation as well as peripheral T cell dysfunction. Deficiency of Klotho, an anti-aging gene and modifier of fibroblast growth factor signaling, causes premature aging. To investigate the role of Klotho in accelerated age-dependent thymic involution, we conducted a comprehensive analysis of thymopoiesis and peripheral T cell homeostasis using Klotho-deficient mice. At 8 weeks of age, Klotho-deficient mice displayed a severe reduction in the number of thymocytes (10–100 fold reduction), especially CD4 and CD8 double positive cells, and a reduction of both cortical and medullary TEC. To address a cell-autonomous role for Klotho in TEC biology, we implanted neonatal thymi from Klotho-deficient and -sufficient mice into athymic hosts. Klotho-deficient thymus grafts supported thymopoiesis equivalently to Klotho-sufficient thymus transplants, indicating that Klotho is not intrinsically essential for TEC support of thymopoiesis. Moreover, lethally-irradiated hosts given Klotho-deficient or WT bone marrow had normal thymocyte development and comparably reconstituted T cells, indicating Klotho is not inherently essential for peripheral T cell reconstitution. Because Klotho-deficient mice have higher levels of serum phosphorus, calcium, and vitamin D, we evaluated thymus function in Klotho-deficient mice fed with vitamin D-deprived diet. We observed that vitamin D-deprived diet abrogated thymic involution and T cell lymphopenia in 8-week-old Klotho-deficient mice. Taken together, our data suggests that Klotho-deficiency causes thymic involution via systemic effects that include high active vitamin D levels.

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Section: Discussionmentioning

confidence: 99%

Thymic Epithelial Cell Support of Thymopoiesis Does Not Require Klotho

Xing

Smith

Goetz

et al. 2018

The Journal of Immunology

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“…which have been attributed to the effect of the sterol on macrophage precursors in vivo [17,18]. Conflicting results have also been reported between in vitro and in vivo studies on the effect of vitamin D compounds on lympho cyte proliferation and IL-2 production [6,7,19].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Therapy Modulates Cytokine Secretion in Patients with Renal Failure

Riancho

Zarrabeitia

Francisco

et al. 1993

Nephron

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In studies in vitro calcitriol (1,25-dihydroxyvitamin D₃) inhibits lymphocyte proliferation and modulates several monocyte functions, including the secretion of prostaglandins and monokines. However its effects on monokine production in vivo are not known. Therefore we studied the secretion of interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMC) from 7 patients on periodic hemodialysis, before and after oral treatment with calcitriol (0.5 μg daily) for 1 month. Calcitriol therapy resulted in significant increases in the phorbol myristate acetate (PMA)-induced secretion of IL-1 and IL-6 (p = 0.04 and 0.03, respectively). This was a transient effect, observable by day 7 of therapy, but no longer evident by day 30. However, calcitriol induced a progressive reduction of TNF secretion (down to 53% of control values by day 30, p = 0.02). There were no correlations between the individual changes in calcium/PTH and cytokine release. These results show that doses of calcitriol within the therapeutic range induce marked changes in cytokine secretion by PBMC from uremic patients.

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“…On a molecular level, 1,25(OH) 2 D 3 leads to reduced expression of HLA class II molecules on endocrine cells (21,22) and inhibits T cell proliferation and the secretion of cytokines (23,24). An effect of vitamin D on thymic education (referred to as 'hormonal imprinting') has been reported in animals (25,26) and lends further support for its immunomodulatory properties. The actions of 1,25(OH) 2 D 3 are mediated via the nuclear vitamin D receptor (VDR).…”

Section: Introductionmentioning

confidence: 93%

Vitamin D receptor genotype is associated with Addison's disease

Pani

Seißler²,

Usadel³

et al. 2002

European Journal of Endocrinology

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Objective: Autoimmune Addison's disease is a rare disorder which results from the T cell-mediated destruction of adrenocortical cells. A number of genetic susceptibility markers are shared by Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis. The vitamin D endocrine system has been shown to influence immune regulation. Variants of the nuclear vitamin D receptor (VDR) gene were found to be associated with type 1 diabetes and thyroid autoimmunity amongst others. We therefore investigated the role of VDR polymorphisms in Addison's disease. Design and methods: Patients ðn ¼ 95Þ and controls ðn ¼ 220Þ were genotyped for VDR polymorphisms Fok I, Bsm I, Apa I and Taq I. Results: The 'ff ' (13.7% vs 5.5%; P ¼ 0:0243; odds ratio = 2.75) and the 'tt' (28.4% vs 14.1%; P ¼ 0:0043; odds ratio = 2.42) genotypes were significantly more frequent in patients than in controls. Furthermore, the Bsm I genotype distribution differed significantly between patients and controls ðx 2 ¼ 6:5016 (2 d.f.) P ¼ 0:0387Þ: Conclusions: These data suggest that the VDR genotype is associated with Addison's disease. The mechanisms by which distinct receptor variants might confer disease susceptibility remain to be elucidated.

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Distinct Target Cells and Effects of lα,25-Dihydroxyvitamin D₃and Glucocorticoids in the Rat Thymus Gland*

Cited by 16 publications

References 26 publications

Thymic Epithelial Cell Support of Thymopoiesis Does Not Require Klotho

Thymic Epithelial Cell Support of Thymopoiesis Does Not Require Klotho

Vitamin D Therapy Modulates Cytokine Secretion in Patients with Renal Failure

Vitamin D receptor genotype is associated with Addison's disease

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Distinct Target Cells and Effects of lα,25-Dihydroxyvitamin D3and Glucocorticoids in the Rat Thymus Gland*

Cited by 16 publications

References 26 publications

Thymic Epithelial Cell Support of Thymopoiesis Does Not Require Klotho

Thymic Epithelial Cell Support of Thymopoiesis Does Not Require Klotho

Vitamin D Therapy Modulates Cytokine Secretion in Patients with Renal Failure

Vitamin D receptor genotype is associated with Addison's disease

Contact Info

Product

Resources

About

Distinct Target Cells and Effects of lα,25-Dihydroxyvitamin D₃and Glucocorticoids in the Rat Thymus Gland*