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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 ; Kreutz, Marina

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 and 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.

Date of publication of this fulltext: 08 Feb 2022 06:27
Article
DOI to cite this document: 10.5283/epub.51590


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-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.



Involved Institutions


Details

Item typeArticle
Journal or Publication TitleScandinavian Journal of Immunology
Publisher:Wiley
Place of Publication:HOBOKEN
Date24 January 2022
InstitutionsMedicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Leibniz Institute for Immunotherapy (LIT)
Identification Number
ValueType
10.1111/sji.13146DOI
KeywordsREGULATORY T-CELLS; VITAMIN-D-RECEPTOR; IMMUNE REGULATION; 1,25-DIHYDROXYVITAMIN D-3; FOXP3 EXPRESSION; DNA METHYLATION; TGF-BETA; IN-VITRO; MECHANISM; EXPANSION;
Dewey Decimal Classification600 Technology > 610 Medical sciences Medicine
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgPartially
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-515900
Item ID51590

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