TY - JOUR
T1 - Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK+ CD8+ T Cells as Conserved Hallmark of Inflammaging
AU - Mogilenko, Denis A.
AU - Shpynov, Oleg
AU - Andhey, Prabhakar Sairam
AU - Arthur, Laura
AU - Swain, Amanda
AU - Esaulova, Ekaterina
AU - Brioschi, Simone
AU - Shchukina, Irina
AU - Kerndl, Martina
AU - Bambouskova, Monika
AU - Yao, Zhangting
AU - Laha, Anwesha
AU - Zaitsev, Konstantin
AU - Burdess, Samantha
AU - Gillfilan, Susan
AU - Stewart-Wigglesworth, Sheila
AU - Colonna, Marco
AU - Artomov, Maksym
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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 (Tem) 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+CD8+ 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.
AB - 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 (Tem) 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+CD8+ 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.
KW - Aging
KW - CD8 T cells
KW - CITE-seq
KW - granzyme K
KW - immune system
KW - inflammaging
KW - single-cell ATAC-sequencing
KW - single-cell BCR-sequencing
KW - single-cell RNA-sequencing
KW - single-cell TCR-sequencing
UR - http://www.scopus.com/inward/record.url?scp=85097512844&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2020.11.005
DO - 10.1016/j.immuni.2020.11.005
M3 - Article
C2 - 33271118
AN - SCOPUS:85097512844
JO - Immunity
JF - Immunity
SN - 1074-7613
ER -