Unknown

Dataset Information

0

1,25D3 prevents CD8(+)Tc2 skewing and asthma development through VDR binding changes to the Cyp11a1 promoter.


ABSTRACT: Effector CD8(+) T cells convert from IFN-γ(+) (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.

SUBMITTER: Schedel M 

PROVIDER: S-EPMC4712703 | biostudies-literature |

REPOSITORIES: biostudies-literature

Shared Molecules

Only show the datasets with similarity scores above: 0.5
     

Similar Datasets

| S-EPMC3657775 | biostudies-literature
| S-EPMC7538595 | biostudies-literature
| S-EPMC2805128 | biostudies-literature
| S-EPMC5925189 | biostudies-literature
| S-EPMC6516584 | biostudies-literature
| S-EPMC9447135 | biostudies-literature
| S-EPMC3133594 | biostudies-literature
| S-EPMC10287919 | biostudies-literature
| S-EPMC3148731 | biostudies-literature
| S-EPMC9235319 | biostudies-literature