Vitamin D controls T cell antigen receptor signaling and activation of human T cells

Nat Immunol. 2010 Apr;11(4):344-9. doi: 10.1038/ni.1851. Epub 2010 Mar 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Enzyme Activation / immunology
  • Humans
  • Immunoblotting
  • In Situ Hybridization
  • Lymphocyte Activation / immunology*
  • Phospholipase C gamma / biosynthesis
  • Phospholipase C gamma / immunology
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Calcitriol / immunology
  • Signal Transduction / immunology*
  • Vitamin D / immunology*

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Calcitriol
  • Vitamin D
  • Phospholipase C gamma