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

Marina Rode von Essen; Martin Kongsbak-Wismann; Peter Schjerling; Klaus Ølgaard; Niels Ødum; Carsten Geisler

doi:10.1038/ni.1851

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

Marina Rode von Essen, Martin Kongsbak-Wismann, Peter Schjerling, Klaus Ølgaard, Niels Ødum, Carsten Geisler

359 Citations (Scopus)

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-_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.

Original language	English
Journal	Nature Immunology
Volume	11
Issue number	4
Pages (from-to)	344-349
Number of pages	5
ISSN	1529-2908
DOIs	https://doi.org/10.1038/ni.1851
Publication status	Published - 2010

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title = "Vitamin D controls T cell antigen receptor signaling and activation of human T cells",

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-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.",

author = "{von Essen}, {Marina Rode} and Martin Kongsbak-Wismann and Peter Schjerling and Klaus {\O}lgaard and Niels {\O}dum and Carsten Geisler",

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",

year = "2010",

doi = "10.1038/ni.1851",

language = "English",

volume = "11",

pages = "344--349",

journal = "Nature Immunology",

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TY - JOUR

T1 - Vitamin D controls T cell antigen receptor signaling and activation of human T cells

AU - von Essen, Marina Rode

AU - Kongsbak-Wismann, Martin

AU - Schjerling, Peter

AU - Ølgaard, Klaus

AU - Ødum, Niels

AU - Geisler, Carsten

N1 - 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

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

U2 - 10.1038/ni.1851

DO - 10.1038/ni.1851

M3 - Journal article

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VL - 11

SP - 344

EP - 349

JO - Nature Immunology

JF - Nature Immunology

IS - 4

ER -

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

Abstract

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