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

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 Stewart-Wigglesworth, Marco Colonna, Maksym Artomov

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalImmunity
DOIs
StateAccepted/In press - 2020

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

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