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Sestrins诱导衰老样CD8 + T细胞的自然杀伤功能
作者:小柯机器人 发布时间:2020/3/31 16:04:36

伦敦大学学院Arne N. Akbar团队取得一项新突破。他们的最新研究发现在衰老样CD8 + T细胞中,Sestrins诱导细胞的自然杀伤功能。2020年3月30日,《自然—免疫学》在线发表了这项成果。

在本研究中,研究人员发现CD27-CD28-CD8 + T细胞丧失了T细胞抗原受体(TCR)信号传导的活性,并表达包含激动性自然杀伤(NK)受体NKG2D和NK衔接子分子DAP12的蛋白复合物,从而增强了对表达NKG2D配体细胞的细胞毒性。

免疫沉淀和成像细胞计数表明,NKG2D–DAP12复合物与sestrin 2有关。抑制sestrin 2降低了衰老样CD27–CD28–CD8 + T细胞中NKG2D和DAP12的表达,并恢复TCR信号传导。因此,在衰老过程中,sestrins诱导非增殖性衰老样CD27-CD28-CD8 + T细胞重编程,从而获得广谱的先天样杀伤活性。

据悉,衰老与免疫系统的重塑有关,以维持终生免疫。在CD8 + T细胞中,衰老会导致具有细胞衰老特征的高分化细胞膨胀。

附:英文原文

Title: Sestrins induce natural killer function in senescent-like CD8 + T cells

Author: Branca I. Pereira, Roel P. H. De Maeyer, Luciana P. Covre, Djamel Nehar-Belaid, Alessio Lanna, Sophie Ward, Radu Marches, Emma S. Chambers, Daniel C. O. Gomes, Natalie E. Riddell, Mala K. Maini, Vitor H. Teixeira, Samuel M. Janes, Derek W. Gilroy, Anis Larbi, Neil A. Mabbott, Duygu Ucar, George A. Kuchel, Sian M. Henson, Jessica Strid, Jun H. Lee, Jacques Banchereau, Arne N. Akbar

Issue&Volume: 2020-03-30

Abstract: Aging is associated with remodeling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, aging results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27CD28CD8+ T cells lost the signaling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic natural killer (NK) receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. Immunoprecipitation and imaging cytometry indicated that the NKG2D–DAP12 complex was associated with sestrin 2. The genetic inhibition of sestrin 2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27CD28CD8+ T cells. Therefore, during aging, sestrins induce the reprogramming of non-proliferative senescent-like CD27CD28CD8+ T cells to acquire a broad-spectrum, innate-like killing activity.

DOI: 10.1038/s41590-020-0643-3

Source: https://www.nature.com/articles/s41590-020-0643-3

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