Physiological levels of 25-hydroxyvitamin D3 induce a suppressive CD4+ T cell phenotype not reflected in the epigenetic landscape
Matos C, Renner K, Peuker A, Schoenhammer G, Schreiber L, Bruss C, Eder R, Bruns H, Flamann C, Hoffmann P, Gebhard C, Herr W, Rehli M, Peter K, Kreutz M (2022)
Publication Type: Journal article
Publication year: 2022
Journal
DOI: 10.1111/sji.13146
Abstract
1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 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)D3) on the differentiation of human CD4+ T cells applying physiological concentrations in vitro. Our data show that 25(OH)D3 is converted to its active form 1,25(OH)2D3 by T cells, which in turn supports FOXP3, CD25 and CTLA-4 expression and inhibits IFN-γ 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-β. Surprisingly, no additive effect but a decreased percentage of FOXP3 expressing cells was observed. However, the combination of 25(OH)D3 or 1,25(OH)2D3 together with TGF-β further upregulated CD25 and CTLA-4 and significantly increased soluble CTLA-4 and IL-10 secretion whereas IFN-γ expression of iTreg was decreased. Our data suggest that physiological levels of 25(OH)D3 act as potent modulator of human CD4+ T cells and autocrine or paracrine production of 1,25(OH)2D3 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)D3 a rather transient phenotype is induced.
Authors with CRIS profile
Heiko Bruns
Department of Medicine 5 – Haematology and Oncology
Cindy Flamann
Department of Medicine 5 – Haematology and Oncology
Involved external institutions
Germany (DE)How to cite
APA:
Matos, C., Renner, K., Peuker, A., Schoenhammer, G., Schreiber, L., Bruss, C.,... Kreutz, M. (2022). Physiological levels of 25-hydroxyvitamin D3 induce a suppressive CD4+ T cell phenotype not reflected in the epigenetic landscape. Scandinavian Journal of Immunology. https://doi.org/10.1111/sji.13146
MLA:
Matos, Carina, et al. "Physiological levels of 25-hydroxyvitamin D3 induce a suppressive CD4+ T cell phenotype not reflected in the epigenetic landscape." Scandinavian Journal of Immunology (2022).
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