Senescent cells suppress macrophage-mediated corpse removal via upregulation of the CD47-QPCT/L axis

Research output: Contribution to journalResearch articleContributedpeer-review


  • Daniela Schloesser - , Boehringer Ingelheim GmbH (Author)
  • Laura Lindenthal - , Max Planck Institute of Biochemistry (Author)
  • Julia Sauer - , Boehringer Ingelheim GmbH (Author)
  • Kyoung Jin Chung - , Institute of Clinical Chemistry and Laboratory Medicine (Author)
  • Triantafyllos Chavakis - , Institute of Clinical Chemistry and Laboratory Medicine (Author)
  • Eva Griesser - , Boehringer Ingelheim GmbH (Author)
  • Praveen Baskaran - , Boehringer Ingelheim GmbH (Author)
  • Ulrike Maier-Habelsberger - , Boehringer Ingelheim GmbH (Author)
  • Katrin Fundel-Clemens - , Boehringer Ingelheim GmbH (Author)
  • Ines Schlotthauer - , Boehringer Ingelheim GmbH (Author)
  • Carolin Kirsten Watson - , Boehringer Ingelheim GmbH (Author)
  • Lee Kim Swee - , Boehringer Ingelheim GmbH (Author)
  • Frederik Igney - , Boehringer Ingelheim GmbH (Author)
  • John Edward Park - , Boehringer Ingelheim GmbH (Author)
  • Markus S. Huber-Lang - , Ulm University (Author)
  • Matthew James Thomas - , Boehringer Ingelheim GmbH (Author)
  • Karim Christian El Kasmi - , Boehringer Ingelheim GmbH (Author)
  • Peter J. Murray - , Max Planck Institute of Biochemistry (Author)


Progressive accrual of senescent cells in aging and chronic diseases is associated with detrimental effects in tissue homeostasis. We found that senescent fibroblasts and epithelia were not only refractory to macrophage-mediated engulfment and removal, but they also paralyzed the ability of macrophages to remove bystander apoptotic corpses. Senescent cell-mediated efferocytosis suppression (SCES) was independent of the senescence-associated secretory phenotype (SASP) but instead required direct contact between macrophages and senescent cells. SCES involved augmented senescent cell expression of CD47 coinciding with increased CD47-modifying enzymes QPCT/L. SCES was reversible by interfering with the SIRPα-CD47-SHP-1 axis or QPCT/L activity. While CD47 expression increased in human and mouse senescent cells in vitro and in vivo, another ITIM-containing protein, CD24, contributed to SCES specifically in human epithelial senescent cells where it compensated for genetic deficiency in CD47. Thus, CD47 and CD24 link the pathogenic effects of senescent cells to homeostatic macrophage functions, such as efferocytosis, which we hypothesize must occur efficiently to maintain tissue homeostasis.


Original languageEnglish
Article numbere202207097
Number of pages29
JournalJournal of Cell Biology
Issue number2
Publication statusPublished - 6 Feb 2023

External IDs

PubMed 36459066
WOS 000927211100001


Sustainable Development Goals

ASJC Scopus subject areas


  • Cancer, Cellular senescence, Clearance, Contributes, Efferocytosis, Mechanism, Metabolism, Secretory phenotype, Target, Up-Regulation, Humans, CD47 Antigen/genetics, Macrophages/cytology, Animals, Aminoacyltransferases/metabolism, CD24 Antigen/metabolism, Mice, Senescence-Associated Secretory Phenotype, Apoptosis

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