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Themis蛋白在CD8+T细胞中的功能
作者:小柯机器人 发布时间:2020/1/15 11:30:11

新加坡国立大学Nicholas R. J. Gascoigne小组的一项最新研究发现,CD8 + T细胞中T细胞受体和细胞因子信号的整合是由Themis蛋白介导的。这一研究成果2020年1月13日在线发表在国际学术期刊《自然—免疫学》上。

利用条件性敲出T细胞谱系特异性蛋白Themis,研究人员发现Themis是维持外周CD8 + T细胞以及CD8 + T细胞应对细胞因子辅助性低亲和力肽-主要组织相容性复合体(pMHC)增殖所必需的。Themis缺失的外周T细胞表现出自身pMHC补体信号传导减少,这表明Themis是T细胞受体信号强度的正向调节剂以响应外周T细胞中低亲和力自身pMHC。仅在Themis存在的条件下,来自低亲和力pMHC和细胞因子的信号协同诱导CD8 + T细胞中Akt激酶的磷酸化、代谢变化和转录因子c-Myc的表达。Themis的这一功能是通过Shp1磷酸酶介导的,因为外周Themis和Shp1的双敲除可促进外周CD8 + T细胞的维持。

据介绍,T细胞稳态和功能发挥需要来自自身肽-主要组织相容性复合体和细胞因子的信号,但调控该信号整合的机制尚不清楚。

附:英文原文

Title: T cell receptor and cytokine signal integration in CD8 + T cells is mediated by the protein Themis

Author: Joanna Brzostek, Namrata Gautam, Xiang Zhao, Elijah W. Chen, Monika Mehta, Desmond W. H. Tung, Yen Leong Chua, Jiawei Yap, Su H. Cho, Shvetha Sankaran, Vasily Rybakin, Guo Fu, Nicholas R. J. Gascoigne

Issue&Volume: 2020-01-13

Abstract: T cell homeostasis and functional responsiveness require signals from self-peptide–major histocompatibility complex (self-pMHC) and cytokines, but the mechanisms controlling this signal integration are unknown. Using a conditional deletion of the T cell lineage-specific protein Themis, we show that Themis is required for the maintenance of peripheral CD8+ T cells and for proliferative CD8+ T cell responses to low-affinity pMHC aided by cytokines. Themis-deficient peripheral T cells show a phenotype indicative of reduced tonic signaling from self-pMHC, strongly suggesting that Themis is a positive regulator of T cell receptor signal strength in response to low-affinity self-pMHC in peripheral T cells. Signals from low-affinity pMHC and cytokines synergistically induce phosphorylation of the kinase Akt, metabolic changes and c-Myc transcription factor induction in CD8+ T cells only in the presence of Themis. This function of Themis is mediated through Shp1 phosphatase, as peripheral Themis and Shp1 double deletion rescues the peripheral CD8+ T cell maintenance.

DOI: 10.1038/s41590-019-0570-3

Source: https://www.nature.com/articles/s41590-019-0570-3

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex