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Physiological levels of 25‐hydroxyvitamin D₃ induce a suppressive CD4⁺ T cell phenotype not reflected in the epigenetic landscape
Matos, Carina
, Renner, Kathrin
, Peuker, Alice, Schoenhammer, Gabriele, Schreiber, Laura, Bruss, Christina, Eder, Ruediger, Bruns, Heiko, Flamann, Cindy, Hoffmann, Petra, Gebhard, Claudia
, Herr, Wolfgang, Rehli, Michael, Peter, Katrin
und Kreutz, Marina
(2022)
Physiological levels of 25‐hydroxyvitamin D₃ induce a suppressive CD4⁺ T cell phenotype not reflected in the epigenetic landscape.
Scandinavian Journal of Immunology.
Veröffentlichungsdatum dieses Volltextes: 08 Feb 2022 06:27
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.51590
Zusammenfassung
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-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.
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| Dokumentenart | Artikel | ||||
| Titel eines Journals oder einer Zeitschrift | Scandinavian Journal of Immunology | ||||
| Verlag: | Wiley | ||||
|---|---|---|---|---|---|
| Ort der Veröffentlichung: | HOBOKEN | ||||
| Datum | 24 Januar 2022 | ||||
| Institutionen | Medizin > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Leibniz-Institut für Immuntherapie (LIT) | ||||
| Identifikationsnummer |
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| Stichwörter / Keywords | REGULATORY T-CELLS; VITAMIN-D-RECEPTOR; IMMUNE REGULATION; 1,25-DIHYDROXYVITAMIN D-3; FOXP3 EXPRESSION; DNA METHYLATION; TGF-BETA; IN-VITRO; MECHANISM; EXPANSION; | ||||
| Dewey-Dezimal-Klassifikation | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status | Veröffentlicht | ||||
| Begutachtet | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden | Zum Teil | ||||
| URN der UB Regensburg | urn:nbn:de:bvb:355-epub-515900 | ||||
| Dokumenten-ID | 51590 |
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