ature Immunology 7 March 2010 | doi:10.1038/ni.1851
Vitamin D controls T cell antigen receptor signaling and activation of human T cells
Marina Rode von Essen1, Martin Kongsbak1, Peter Schjerling2,4, Klaus Olgaard5, Niels ?dum1,3 & Carsten Geisler1
Phospholipase C (PLC) isozymes are key signaling proteins downstream of many extracellular stimuli. Here we show that naive human T cells had very low expression of PLC-γ1 and that this correlated with low T cell antigen receptor (TCR) responsiveness in naive T cells. However, TCR triggering led to an upregulation of ~75-fold in PLC-γ1 expression, which correlated with greater TCR responsiveness. Induction of PLC-γ1 was dependent on vitamin D and expression of the vitamin D receptor (VDR). Naive T cells did not express VDR, but VDR expression was induced by TCR signaling via the alternative mitogen-activated protein kinase p38 pathway. Thus, initial TCR signaling via p38 leads to successive induction of VDR and PLC-γ1, which are required for subsequent classical TCR signaling and T cell activation.
1 Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
2 Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
3 Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
4 Institute of Sports Medicine, Bispebjerg Hospital, Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark.
5 Department of Nephrology, Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark.