Single-cell atlas of healthy human blood unveils age-related loss of NKG2C + GZMB - CD8 + memory T cells and accumulation of type 2 memory T cells.

Autor: Terekhova M; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Swain A; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Bohacova P; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Aladyeva E; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Arthur L; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Laha A; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Mogilenko DA; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Medicine, Department of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Burdess S; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Sukhov V; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Computer Technologies Laboratory, ITMO University, Saint Petersburg 197101, Russia., Kleverov D; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Computer Technologies Laboratory, ITMO University, Saint Petersburg 197101, Russia., Echalar B; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Tsurinov P; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; JetBrains Research, 8021 Paphos, Cyprus., Chernyatchik R; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; JetBrains Research, 80639 Munich, Germany., Husarcikova K; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Artyomov MN; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: martyomov@wustl.edu.
Jazyk: angličtina
Zdroj: Immunity [Immunity] 2023 Dec 12; Vol. 56 (12), pp. 2836-2854.e9. Date of Electronic Publication: 2023 Nov 13.
DOI: 10.1016/j.immuni.2023.10.013
Abstrakt: Extensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for the systematic understanding of human aging. Here, using single-cell RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 healthy individuals aged 25-85 years old. From this, we generated a dataset from ∼2 million cells that described 55 subpopulations of blood immune cells. Twelve subpopulations changed with age, including the accumulation of GZMK + CD8 + T cells and HLA-DR + CD4 + T cells. In contrast to other T cell memory subsets, transcriptionally distinct NKG2C + GZMB - CD8 + T cells counterintuitively decreased with age. Furthermore, we found a concerted age-associated increase in type 2/interleukin (IL)4-expressing memory subpopulations across CD4 + and CD8 + T cell compartments (CCR4 + CD8 + Tcm and Th2 CD4 + Tmem), suggesting a systematic functional shift in immune homeostasis with age. Our work provides novel insights into healthy human aging and a comprehensive annotated resource.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE