硒蛋白在衰老样CD8 T细胞中诱导自然杀伤功能。
Sestrins induce natural killer function in senescent-like CD8 T cells.
作者信息
Pereira Branca I, De Maeyer Roel P H, Covre Luciana P, Nehar-Belaid Djamel, Lanna Alessio, Ward Sophie, Marches Radu, Chambers Emma S, Gomes Daniel C O, Riddell Natalie E, Maini Mala K, Teixeira Vitor H, Janes Samuel M, Gilroy Derek W, Larbi Anis, Mabbott Neil A, Ucar Duygu, Kuchel George A, Henson Sian M, Strid Jessica, Lee Jun H, Banchereau Jacques, Akbar Arne N
机构信息
Division of Infection and Immunity, University College London, London, UK.
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.
出版信息
Nat Immunol. 2020 Jun;21(6):684-694. doi: 10.1038/s41590-020-0643-3. Epub 2020 Mar 30.
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.
衰老与免疫系统重塑相关，以维持终身免疫。在CD8 T细胞区室中，衰老导致高度分化细胞的扩增，这些细胞表现出细胞衰老的特征。在这里，我们发现CD27CD28CD8 T细胞失去了T细胞抗原受体（TCR）的信号活性，并表达了一种包含激动性自然杀伤（NK）受体NKG2D和NK衔接分子DAP12的蛋白复合物，该复合物促进了对表达NKG2D配体的细胞的细胞毒性。免疫沉淀和成像细胞术表明，NKG2D-DAP12复合物与 sestrin 2相关。sestrin 2的基因抑制导致NKG2D和DAP12的表达降低，并恢复了衰老样CD27CD28CD8 T细胞中的TCR信号。因此，在衰老过程中， sestrins诱导非增殖性衰老样CD27CD28CD8 T细胞重编程，以获得广谱的、类似先天免疫的杀伤活性。
Zotero 插件