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Tim-3表达上调促进小鼠烧伤诱导的T细胞免疫抑制的发展。

Up-regulation of Tim-3 expression contributes to development of burn-induced T cell immune suppression in mice.

作者信息

Tang Zhaohui, Yu Yan, Qiu Wenhong, Zhang Jian, Yang Xiangping

机构信息

Department of Trauma Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2011 Oct;31(5):642. doi: 10.1007/s11596-011-0575-0. Epub 2011 Oct 25.

Abstract

T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3(+) T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4(+) and CD8(+) T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3(+) T cells subsets were more prone to spontaneous apoptosis than Tim-3(-) T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.

摘要

T细胞免疫球蛋白和粘蛋白结构域3(Tim-3)对T细胞反应具有负向调节作用,这一点已广为人知,但其在烧伤诱导的T细胞免疫抑制中的作用仍不清楚。在本研究中,为了明确Tim-3表达与烧伤后T细胞免疫抑制之间的关系,对C57BL/6小鼠进行烧伤或假手术损伤,并在术后第1天采集肝脏和脾脏。评估肝脏或脾脏T细胞上Tim-3的表达水平以及Tim-3(+) T细胞的功能特性。结果发现,与烧伤后T细胞耗竭相反,烧伤损伤导致肝脏和脾脏CD4(+)和CD8(+) T细胞上Tim-3表达显著升高。此外,Tim-3表达与烧伤后T细胞的抑制表型相关,包括抗炎细胞因子IL-10表达增加、促炎细胞因子IFN-γ和TNF-α表达降低、T细胞增殖减少以及Tim-3和PD-1共表达升高。而且,Tim-3(+) T细胞亚群比Tim-3(-) T细胞亚群更容易发生自发凋亡。我们的研究结果强化了这样一种观点,即烧伤后T细胞上Tim-3表达上调在烧伤诱导的T细胞免疫抑制的发生和维持中起重要作用。

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