Vitamin D controls T cell antigen receptor signaling and activation of human T cells.
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-gamma1 and that this correlated with low T cell antigen receptor (TCR) responsiveness in naive T cells. However, TCR triggering led to an upregulation of approximately 75-fold in PLC-gamma1 expression, which correlated with greater TCR responsiveness. Induction of PLC-gamma1 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-gamma1, which are required for subsequent classical TCR signaling and T cell activation.
von Essen
Marina Rode
MR
Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Kongsbak
Martin
M
Schjerling
Peter
P
Olgaard
Klaus
K
Odum
Niels
N
Geisler
Carsten
C
D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D008213:Lymphocyte Activation / Q000276:immunology*; D051966:Phospholipase C gamma / Q000096:biosynthesis / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D018167:Receptors, Calcitriol / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014807:Vitamin D / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D018167:Receptors, Calcitriol; D014807:Vitamin D; D051966:Phospholipase C gamma