Matos, Carina and Renner, Kathrin and Peuker, Alice and Schoenhammer, Gabriele and Schreiber, Laura and Bruss, Christina and Eder, Ruediger and Bruns, Heiko and Flamann, Cindy and Hoffmann, Petra and Gebhard, Claudia and Herr, Wolfgang and Rehli, Michael and Peter, Katrin and Kreutz, Marina (2022) Physiological levels of 25-hydroxyvitamin D-3 induce a suppressive CD4(+)T cell phenotype not reflected in the epigenetic landscape. SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 95 (5): e13146. ISSN 0300-9475, 1365-3083
Full text not available from this repository. (Request a copy)Abstract
1,25-dihydroxyvitamin D3 (1,25(OH)(2)D-3), the active metabolite of vitamin D3 has a strong impact on the differentiation and function of immune cells. Here we analysed the influence of its precursor 25-hydroxyvitamin D3 (25(OH)D-3) on the differentiation of human CD4(+) T cells applying physiological concentrations in vitro. Our data show that 25(OH)D-3 is converted to its active form 1,25(OH)(2)D-3 by T cells, which in turn supports FOXP3, CD25 and CTLA-4 expression and inhibits IFN-gamma production. These changes were not reflected in the demethylation of the respective promoters. Furthermore, we investigated the impact of vitamin D3 metabolites under induced Treg (iTreg) polarization conditions using TGF-beta. Surprisingly, no additive effect but a decreased percentage of FOXP3 expressing cells was observed. However, the combination of 25(OH)D-3 or 1,25(OH)(2)D-3 together with TGF-beta further upregulated CD25 and CTLA-4 and significantly increased soluble CTLA-4 and IL-10 secretion whereas IFN-gamma expression of iTreg was decreased. Our data suggest that physiological levels of 25(OH)D-3 act as potent modulator of human CD4(+)T cells and autocrine or paracrine production of 1,25(OH)(2)D-3 by T cells might be crucial for the local regulation of an adaptive immune response. However, since no epigenetic changes are detected by 25(OH)D-3 a rather transient phenotype is induced.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T-CELLS; VITAMIN-D-RECEPTOR; IMMUNE REGULATION; 1,25-DIHYDROXYVITAMIN D-3; FOXP3 EXPRESSION; DNA METHYLATION; TGF-BETA; IN-VITRO; MECHANISM; EXPANSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Dec 2023 14:51 |
| Last Modified: | 05 Dec 2023 14:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56936 |
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