Schedel, Michaela and Jia, Yi and Michel, Sven and Takeda, Katsuyuki and Domenico, Joanne and Joetham, Anthony and Ning, Fangkun and Strand, Matthew and Han, Junyan and Wang, Meiqin and Lucas, Joseph J. and Vogelberg, Christian and Kabesch, Michael and O'Connor, Brian P. and Gelfand, Erwin W. (2016) 1,25D3 prevents CD8(+) Tc2 skewing and asthma development through VDR binding changes to the Cyp11a1 promoter. NATURE COMMUNICATIONS, 7: 10213. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
Effector CD8(+) T cells convert from IFN-gamma(+) (Tc1) to IL-13(+) (Tc2) cells in the presence of IL-4. Underlying regulatory mechanisms are not fully defined. Here, we show that addition of 1,25D3, the active form of vitamin D3, during CD8(+) T-cell differentiation prevents IL-4-induced conversion to IL-13-producers. Transfer of 1,25D3-treated CD8(+) T cells into sensitized and challenged CD8(+)-deficient recipients fails to restore development of lung allergic responses. 1,25D3 alters vitamin D receptor (VDR) recruitment to the Cyp11a1 promoter in vitro and in vivo in the presence of IL-4. As a result, protein levels and enzymatic activity of CYP11A1, a steroidogenic enzyme regulating CD8(+) T-cell conversion, are decreased. An epistatic effect between CYP11A1 and VDR polymorphisms may contribute to the predisposition to childhood asthma. These data identify a role for 1,25D3 in the molecular programming of CD8(+) T-cell conversion to an IL-13-secreting phenotype through regulation of steroidogenesis, potentially governing asthma susceptibility.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MEDIATED AIRWAY HYPERRESPONSIVENESS; STEROIDOGENIC ENZYME CYP11A1; RECEPTOR GENE POLYMORPHISMS; VITAMIN-D LEVELS; T-CELLS; ADULT ASTHMA; LEUKOTRIENE B-4; LUNG-FUNCTION; 25-HYDROXYVITAMIN D-3; MULTIPLE-SCLEROSIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Mar 2019 12:36 |
| Last Modified: | 07 Mar 2019 08:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2203 |
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