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

Schedel M, Jia Y, Michel S, Takeda K, Domenico J, Joetham A, Ning F, Strand M, Han J, Wang M, Lucas JJ, Vogelberg C, Kabesch M, O'Connor BP, Gelfand EW.
Nature communications. 2016;7:10213.
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.
Consortium data used in this publication
ENCODE TF ChIP, DNase, Histone modification ChIP, chromatin states, RegulomeDB, table S3
References