-
Tytuł:
-
Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK T Cells as Conserved Hallmark of Inflammaging.
-
Autorzy:
-
Mogilenko DA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Shpynov O; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; JetBrains Research, Saint Petersburg 197374, Russia.
Andhey PS; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Arthur L; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Swain A; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Esaulova E; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Brioschi S; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Shchukina I; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kerndl M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Institute for Vascular Biology, Centre for Physiology and Pharmacology & Christian Doppler Laboratory for Arginine Metabolism in Rheumatoid Arthritis and Multiple Sclerosis, Vienna 1090, Austria.
Bambouskova M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Yao Z; Department of Cell Biology and Physiology, Department of Medicine and Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Laha A; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Zaitsev K; Computer Technologies Department, ITMO University, Saint Petersburg 197101, Russia.
Burdess S; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gillfilan S; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Stewart SA; Department of Cell Biology and Physiology, Department of Medicine and Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Colonna M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Artyomov MN; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: .
-
Źródło:
-
Immunity [Immunity] 2021 Jan 12; Vol. 54 (1), pp. 99-115.e12. Date of Electronic Publication: 2020 Dec 02.
-
Typ publikacji:
-
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
-
Język:
-
English
-
Imprint Name(s):
-
Publication: Cambridge, MA : Cell Press
Original Publication: Cambridge, Mass. : Cell Press, c1994-
-
MeSH Terms:
-
Aging/*physiology
CD8-Positive T-Lymphocytes/*physiology
Immune System/*physiology
Inflammation/*immunology
Receptors, Antigen, B-Cell/*genetics
Receptors, Antigen, T-Cell/*genetics
Animals ; Cells, Cultured ; Clone Cells ; Cytotoxicity, Immunologic ; Female ; Gene Expression Profiling ; Granzymes/metabolism ; Humans ; Immunologic Memory ; Mice ; Mice, Inbred C57BL ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome
-
Contributed Indexing:
-
Keywords: Aging; CD8 T cells; CITE-seq; granzyme K; immune system; inflammaging; single-cell ATAC-sequencing; single-cell BCR-sequencing; single-cell RNA-sequencing; single-cell TCR-sequencing
-
Substance Nomenclature:
-
0 (Receptors, Antigen, B-Cell)
0 (Receptors, Antigen, T-Cell)
EC 3.4.21.- (Granzymes)
-
Entry Date(s):
-
Date Created: 20201203 Date Completed: 20210909 Latest Revision: 20210909
-
Update Code:
-
20240104
-
DOI:
-
10.1016/j.immuni.2020.11.005
-
PMID:
-
33271118
-
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.
Competing Interests: Declaration of Interests The authors declare no competing interests.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Comment in: Nat Rev Immunol. 2021 Jan;21(1):1. (PMID: 33303954)
Comment in: Immunity. 2021 Jan 12;54(1):6-8. (PMID: 33440137)
