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

被引：369

作者：

Mogilenko, Denis A. ^{[1
]}

Shpynov, Oleg ^{[1
,2
]}

Andhey, Prabhakar Sairam ^{[1
]}

Arthur, Laura ^{[1
]}

Swain, Amanda ^{[1
]}

Esaulova, Ekaterina ^{[1
]}

Brioschi, Simone ^{[1
]}

Shchukina, Irina ^{[1
]}

Kerndl, Martina ^{[1
,3
,4
]}

Bambouskova, Monika ^{[1
]}

Yao, Zhangting ^{[5
,6
]}

Laha, Anwesha ^{[1
]}

Zaitsev, Konstantin ^{[7
]}

Burdess, Samantha ^{[1
]}

Gillfilan, Susan ^{[1
]}

Stewart, Sheila A. ^{[5
,6
]}

Colonna, Marco ^{[1
]}

Artyomov, Maxim N. ^{[1
]}

机构：

[1] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA

[2] JetBrains Res, St Petersburg 197374, Russia

[3] Ctr Physiol & Pharmacol, Inst Vasc Biol, A-1090 Vienna, Austria

[4] Christian Doppler Lab Arginine Metab Rheumatoid A, A-1090 Vienna, Austria

[5] Washington Univ, Sch Med, Dept Cell Biol & Physiol, Dept Med, St Louis, MO 63110 USA

[6] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA

[7] ITMO Univ, Comp Technol Dept, St Petersburg 197101, Russia

来源：

IMMUNITY | 2021年 / 54卷 / 01期

关键词：

GRANZYME K; AGED MICE; HETEROGENEITY; VARIABILITY; RESPONSES; SUBSETS;

D O I：

10.1016/j.immuni.2020.11.005

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Systematic understanding of immune aging on a whole-body scale is currently lacking. We characterized age-associated alterations in immune cells across multiple mouse organs using single-cell RNA and antigen receptor sequencing and flow cytometry-based validation. We defined organ-specific and common immune alterations and identified a subpopulation of age-associated granzyme K (GZMK)-expressing CD8(+) T (Taa) cells that are distinct from T effector memory (Tern) cells. Taa cells were highly clonal, had specific epigenetic and transcriptional signatures, developed in response to an aged host environment, and expressed markers of exhaustion and tissue homing. Activated Taa cells were the primary source of GZMK, which enhanced inflammatory functions of non-immune cells. In humans, proportions of the circulating GZMK(+) CDE3(+) T cell population that shares transcriptional and epigenetic signatures with mouse Taa cells increased during healthy aging. These results identify GZMK(+) Taa cells as a potential target to address age-associated dysfunctions of the immune system.

引用

页码：99 / +

页数：29

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