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维生素 D 控制 T 细胞抗原受体信号和人类 T 细胞的激活。

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

机构信息

Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

出版信息

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

DOI:10.1038/ni.1851
PMID:20208539
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.

摘要

磷酸脂酶 C（PLC）同工酶是许多细胞外刺激的关键信号蛋白。在这里，我们发现幼稚人 T 细胞中 PLC-γ1 的表达水平非常低，这与幼稚 T 细胞中 T 细胞抗原受体（TCR）的低反应性相关。然而，TCR 的触发导致 PLC-γ1 的表达上调了约 75 倍，这与更高的 TCR 反应性相关。PLC-γ1 的诱导依赖于维生素 D 和维生素 D 受体（VDR）的表达。幼稚 T 细胞不表达 VDR，但 TCR 信号通过替代丝裂原活化蛋白激酶 p38 途径诱导 VDR 的表达。因此，最初的 TCR 信号通过 p38 导致 VDR 和 PLC-γ1 的连续诱导，这是随后的经典 TCR 信号和 T 细胞激活所必需的。

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本文引用的文献

[1]
On the mechanism underlying (23S)-25-dehydro-1alpha(OH)-vitamin D3-26,23-lactone antagonism of hVDRwt gene activation and its switch to a superagonist.

J Biol Chem. 2009-9-28

[2]
T cell receptor-mediated activation of p38{alpha} by mono-phosphorylation of the activation loop results in altered substrate specificity.

J Biol Chem. 2009-6-5

[3]
Immunomodulation by a novel, dissociated Vitamin D analogue.

Exp Dermatol. 2009-7

[4]
T cell activation.

Annu Rev Immunol. 2009

[5]
Failure of T cell homing, reduced CD4/CD8alphaalpha intraepithelial lymphocytes, and inflammation in the gut of vitamin D receptor KO mice.

Proc Natl Acad Sci U S A. 2008-12-30

[6]
TCR down-regulation controls virus-specific CD8+ T cell responses.

J Immunol. 2008-12-1

[7]
Tentative T cells: memory cells are quick to respond, but slow to divide.

PLoS Pathog. 2008-4-11

[8]
The vitamin D receptor is required for iNKT cell development.

Proc Natl Acad Sci U S A. 2008-4-1

[9]
The biochemistry of somatic hypermutation.

Annu Rev Immunol. 2008

[10]
Extracellular calcium-sensing receptor activation induces vitamin D receptor levels in proximal kidney HK-2G cells by a mechanism that requires phosphorylation of p38alpha MAPK.

J Biol Chem. 2008-1-4

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