Transcriptional Profiling of γδ T Cells Identifies a Role for Vitamin D in the Immunoregulation of the Vγ9Vδ2 Response to Phosphate-Containing Ligands

摘要: Vitamin D is a steroid hormone that, in addition to its well-characterized role calcium/phosphate metabolism, has been found have regulatory properties for immune system function. The nuclear vitamin receptor widely expressed tissues, but also shown be regulated by hormones, growth factors, and cytokines. In this study we show that activation of human Vdelta2Vgamma9 T cells nonpeptidic monoalkyl phosphates such as isopentenyl pyrophosphate leads the up-regulation via pathway involves classical isoforms protein kinase C. We further active demonstrating ligand 1alpha,25-dihydroxyvitamin D3 (vitD3) significantly inhibits dose-dependent fashion phospholigand-induced gammadelta cell expansion, IFN-gamma production, CD25 expression. vitD3 negatively regulates signaling Akt ERK and, at high concentrations, potentiates Ag-induced death. As such, these data provide support immunoregulatory D, suggest ability regulate proinflammatory activity may contribute protection affords against inflammatory autoimmune disorders dependent upon Th1-type responses.