Impaired Vitamin D Signaling in T Cells From a Family With Hereditary Vitamin D Resistant Rickets.

ABSTRACT: The active form of vitamin D, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), mediates its immunomodulatory effects by binding to the vitamin D receptor (VDR). Here, we describe a new point mutation in the DNA-binding domain of the VDR and its consequences for 1,25(OH)₂D₃ signaling in T cells from heterozygous and homozygous carriers of the mutation. The mutation did not affect the overall structure or the ability of the VDR to bind 1,25(OH)₂D₃ and the retinoid X receptor. However, the subcellular localization of the VDR was strongly affected and the transcriptional activity was abolished by the mutation. In heterozygous carriers of the mutation, 1,25(OH)₂D₃-induced gene regulation was reduced by ~ 5

SUBMITTER: Al-Jaberi FAH 

PROVIDER: S-EPMC8170129 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature