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钙网蛋白对外周T细胞激活的调节

Regulation of peripheral T cell activation by calreticulin.

作者信息

Porcellini Simona, Traggiai Elisabetta, Schenk Ursula, Ferrera Denise, Matteoli Michela, Lanzavecchia Antonio, Michalak Marek, Grassi Fabio

机构信息

Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.

出版信息

J Exp Med. 2006 Feb 20;203(2):461-71. doi: 10.1084/jem.20051519.

DOI:10.1084/jem.20051519
PMID:16492806
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2118200/
Abstract

Regulated expression of positive and negative regulatory factors controls the extent and duration of T cell adaptive immune response preserving the organism's integrity. Calreticulin (CRT) is a major Ca2+ buffering chaperone in the lumen of the endoplasmic reticulum. Here we investigated the impact of CRT deficiency on T cell function in immunodeficient mice reconstituted with fetal liver crt-/- hemopoietic progenitors. These chimeric mice displayed severe immunopathological traits, which correlated with a lower threshold of T cell receptor (TCR) activation and exaggerated peripheral T cell response to antigen with enhanced secretion of inflammatory cytokines. In crt-/- T cells TCR stimulation induced pulsatile cytosolic elevations of Ca2+ concentration and protracted accumulation of nuclear factor of activated T cells in the nucleus as well as sustained activation of the mitogen-activated protein kinase pathways. These observations support the hypothesis that CRT-dependent shaping of Ca2+ signaling critically contributes to the modulation of the T cell adaptive immune response.

摘要

正负调节因子的调控表达控制着T细胞适应性免疫反应的程度和持续时间，从而维护机体的完整性。钙网蛋白（CRT）是内质网腔中主要的Ca2+缓冲伴侣蛋白。在此，我们研究了CRT缺陷对用胎肝crt-/-造血祖细胞重建的免疫缺陷小鼠中T细胞功能的影响。这些嵌合小鼠表现出严重的免疫病理特征，这与T细胞受体（TCR）激活阈值降低以及外周T细胞对抗原的反应过度且炎症细胞因子分泌增加有关。在crt-/-T细胞中，TCR刺激诱导Ca2+浓度的脉动性胞质升高、活化T细胞核因子在细胞核中的长期积累以及丝裂原活化蛋白激酶途径的持续激活。这些观察结果支持以下假设，即依赖CRT的Ca2+信号塑造对T细胞适应性免疫反应的调节起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/792314bbd6ba/jem2030461f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/834c161c1efb/jem2030461f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/11c334f3f695/jem2030461f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/4bfdfb858dce/jem2030461f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/924915f5697a/jem2030461f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/4f1509629dcd/jem2030461f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/fbd2af66d93e/jem2030461f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/3cb7c73f0d76/jem2030461f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/792314bbd6ba/jem2030461f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/834c161c1efb/jem2030461f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/11c334f3f695/jem2030461f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/4bfdfb858dce/jem2030461f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/924915f5697a/jem2030461f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/4f1509629dcd/jem2030461f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/fbd2af66d93e/jem2030461f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/3cb7c73f0d76/jem2030461f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7103/2118200/792314bbd6ba/jem2030461f08.jpg

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