Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3

Kento Takaya, Toru Asou, Kazuo Kishi

Research output: Contribution to journalArticlepeer-review

Abstract

The accumulation of senescent cells in aging tissues is associated with age-related diseases and functional decline. Thus, senolysis, a therapy aimed at rejuvenation by removing senescent cells from the body, is being developed. However, this therapy requires the identification of membrane surface antigens that are specifically expressed on senescent cells for their selective elimination. We showed that atypical chemokine receptor 3 (ACKR3), a receptor of the CXC motif chemokine 12 (CXCL12) implicated in cancer, inflammation, and cardiovascular disorders, is selectively expressed on the surface of senescent human fibroblasts but not on proliferating cells. Importantly, the differential presence of ACKR3 enabled the isolation of senescent cells by flow cytometry using anti-ACKR3 antibodies. Furthermore, antibody-dependent cellular cytotoxicity assays revealed that cell surface ACKR3 preferentially sensitizes senescent but not dividing fibroblasts to cell injury by natural killer cells. Conclusively, the selective expression of ACKR3 on the surface of senescent cells allows the preferential elimination of senescent cells. These results might contribute to the future development of novel senolysis approaches.

Original languageEnglish
Article number6531
JournalInternational journal of molecular sciences
Volume23
Issue number12
DOIs
Publication statusPublished - 2022 Jun 1

Keywords

  • antibody-dependent cellular cytotoxicity
  • atypical chemokine receptor 3
  • fibroblast
  • natural killer cell
  • senolysis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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