新研究利用蛋白質組學解析T細胞分化過程



本期文章:《自然—免疫學》:Online/在線發表

T細胞分化過程中蛋白質組和環境感受器的定量分析,這一成果由英國鄧迪大學Doreen A. Cantrell和Angus I. Lamond等研究人員合作取得。2019年10月7日,《自然—免疫學》雜志在線發表了該研究成果。

通過定量質譜分析,研究人員揭示了CD4陽性和CD8陽性T細胞如何重塑蛋白質組以響應抗原和哺乳動物雷帕霉素靶標復合物1(mTORC1)。分析每個細胞中超過9000種蛋白質的拷貝數可提供對T細胞表型的新認識,從而揭示了影響T細胞命運的代謝和蛋白質合成機制以及環境傳感器。

研究人員揭示了淋巴細胞環境感應是由免疫激活控制的,并且CD4陽性和CD8陽性T細胞在其固有的營養轉運和生物合成能力方面有所不同。這些數據還揭示了對初始T細胞與效應T細胞中mTORC1進行抑制所產生的相同和不同結果:mTORC1抑制會損害活化的初始細胞而非效應細胞中的細胞周期進程,而新陳代謝在這兩個群體中均受到影響。

這項研究提供了初始和效應T細胞蛋白質組的全面圖譜,以及探索和理解T細胞表型和mTORC1功能的資源。

附:英文原文

Title: Quantitative analysis of T cell proteomes and environmental sensors during T cell differentiation

Author: Andrew J. M. Howden, Jens L. Hukelmann, Alejandro Brenes, Laura Spinelli, Linda V. Sinclair, Angus I. Lamond, Doreen A. Cantrell

Issue&Volume: 2019-10-07

Abstract: 

Quantitative mass spectrometry reveals how CD4+ and CD8+ T cells restructure proteomes in response to antigen and mammalian target of rapamycin complex 1 (mTORC1). Analysis of copy numbers per cell of >9,000 proteins provides new understanding of T cell phenotypes, exposing the metabolic and protein synthesis machinery and environmental sensors that shape T cell fate. We reveal that lymphocyte environment sensing is controlled by immune activation, and that CD4+ and CD8+ T cells differ in their intrinsic nutrient transport and biosynthetic capacity. Our data also reveal shared and divergent outcomes of mTORC1 inhibition in naïve versus effector T cells: mTORC1 inhibition impaired cell cycle progression in activated naïve cells, but not effector cells, whereas metabolism was consistently impacted in both populations. This study provides a comprehensive map of naïve and effector T cell proteomes, and a resource for exploring and understanding T cell phenotypes and cell context effects of mTORC1.

DOI: 10.1038/s41590-019-0495-x

Source: https://www.nature.com/articles/s41590-019-0495-x

期刊信息

Nature Immunology:《自然—免疫學》,創刊于2000年。隸屬于施普林格·自然出版集團,最新IF:23.53
官方網址:https://www.nature.com/ni/
投稿鏈接:https://mts-ni.nature.com/cgi-bin/main.plex




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