小柯机器人

美国华盛顿大学医学院Maxim N. Artyomov小组发现，GZMK⁺CD8⁺T细胞是炎性衰老的保守标志。2020年12月2日，国际知名学术期刊《免疫》在线发表了这一成果。

通过使用单细胞RNA和抗原受体测序以及基于流式细胞仪的验证，研究人员在多个小鼠器官的免疫细胞中表征了年龄相关的变化。研究人员定义了器官特异性和常见的免疫改变，并鉴定了年龄相关粒酶K（GZMK）表达CD8⁺T（Taa）细胞的亚群，这些细胞不同于T效应记忆（Tem）细胞。 Taa细胞是高度克隆的，具有特定的表观遗传学和转录特征，可响应衰老的宿主环境而发育，并表达耗竭和组织归巢的标志。活化的Taa细胞是GZMK的主要来源，GZMK增强了非免疫细胞的炎症功能。

在人类中，健康的衰老过程中循环GZMK⁺CD8⁺T细胞群的比例会增加，这些细胞与小鼠Taa细胞具有相似转录和表观遗传学特征。这些结果确定了GZMK⁺Taa细胞是解决免疫系统与年龄相关功能障碍的潜在靶标。

据悉，当前缺乏对全身免疫衰老的系统理解。

附：英文原文

Title: Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK+ CD8+ T Cells as Conserved Hallmark of Inflammaging

Author: Denis A. Mogilenko, Oleg Shpynov, Prabhakar Sairam Andhey, Laura Arthur, Amanda Swain, Ekaterina Esaulova, Simone Brioschi, Irina Shchukina, Martina Kerndl, Monika Bambouskova, Zhangting Yao, Anwesha Laha, Konstantin Zaitsev, Samantha Burdess, Susan Gillfilan, Sheila A. Stewart, Marco Colonna, Maxim N. Artyomov

Issue&Volume: 2020-12-02

Abstract: Systematic understanding of immune aging on a whole-body scale is currently lacking.We characterized age-associated alterations in immune cells across multiple mouseorgans using single-cell RNA and antigen receptor sequencing and flow cytometry-basedvalidation. We defined organ-specific and common immune alterations and identifieda subpopulation of age-associated granzyme K (GZMK)-expressing CD8+ T (Taa) cells that are distinct from T effector memory (Tem) cells. Taa cells werehighly clonal, had specific epigenetic and transcriptional signatures, developed inresponse to an aged host environment, and expressed markers of exhaustion and tissuehoming. Activated Taa cells were the primary source of GZMK, which enhanced inflammatoryfunctions of non-immune cells. In humans, proportions of the circulating GZMK+CD8+ T cell population that shares transcriptional and epigenetic signatures with mouseTaa cells increased during healthy aging. These results identify GZMK+ Taa cells as a potential target to address age-associated dysfunctions of the immunesystem.

DOI: 10.1016/j.immuni.2020.11.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30492-1

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