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Physiological levels of 25‐hydroxyvitamin D 3 induce a suppressive CD4 + T cell phenotype not reflected in the epigenetic landscape
Author(s) -
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
Publication year - 2022
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.13146
Subject(s) - il 2 receptor , immune system , autocrine signalling , paracrine signalling , foxp3 , ctla 4 , chemistry , medicine , t cell , biology , endocrinology , microbiology and biotechnology , immunology , biochemistry , receptor
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‐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)D 3 or 1,25(OH) 2 D 3 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)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.