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

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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.
Original languageEnglish
JournalNature Immunology
Volume11
Issue number4
Pages (from-to)344-349
Number of pages5
ISSN1529-2908
DOIs
Publication statusPublished - 2010

Bibliographical note

Keywords: Cells, Cultured; Enzyme Activation; Humans; Immunoblotting; In Situ Hybridization; Lymphocyte Activation; Phospholipase C gamma; Receptors, Antigen, T-Cell; Receptors, Calcitriol; Signal Transduction; Vitamin D

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