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Nat Commun. 2016 Jan 11;7:10213. doi: 10.1038/ncomms10213.

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

Author information

Division of Cell Biology, Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, USA.
University Children's Hospital Regensburg (KUNO), Department of Pediatric Pneumology and Allergy, Steinmetzstrasse 1-3, 93049 Regensburg, Germany.
Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Carl-Neuberg-Strasse, 30625 Hannover, Germany.
Division of Biostatistics and Bioinformatics, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, USA.
Department of Pediatrics, University Children's Hospital, Technical University, Fetscherstraße 74, 01307 Dresden, Germany.
Center for Genes, Environment and Health, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, USA.
Department of Immunology and Microbiology, University of Colorado AMC, 13001 E 17th Place, Aurora, Colorado 80045, USA.


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.

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