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Liebold, Imke; Al Jawazneh, Amirah; Casar, Christian; Lanzloth, Clarissa; Leyk, Stephanie; Hamley, Madeleine; Wong, Milagros N.; Kylies, Dominik; Gräfe, Stefanie K.; Edenhofer, Ilka; Aranda-Pardos, Irene; Kriwet, Marie; Haas, Helmuth; Krause, Jenny; Hadjilaou, Alexandros; Schromm, Andra B.; Richardt, Ulricke; Eggert, Petra; Tappe, Dennis; Weidemann, Sören A.; Ghosh, Sourav; Krebs, Christian F.; A-Gonzalez, Noelia; Worthmann, Anna; [...]

Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages

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  • Media type: E-Article
  • Title: Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages
  • Contributor: Liebold, Imke; Al Jawazneh, Amirah; Casar, Christian; Lanzloth, Clarissa; Leyk, Stephanie; Hamley, Madeleine; Wong, Milagros N.; Kylies, Dominik; Gräfe, Stefanie K.; Edenhofer, Ilka; Aranda-Pardos, Irene; Kriwet, Marie; Haas, Helmuth; Krause, Jenny; Hadjilaou, Alexandros; Schromm, Andra B.; Richardt, Ulricke; Eggert, Petra; Tappe, Dennis; Weidemann, Sören A.; Ghosh, Sourav; Krebs, Christian F.; A-Gonzalez, Noelia; Worthmann, Anna; [...]
  • Published: American Association for the Advancement of Science (AAAS), 2024
  • Published in: Science, 384 (2024) 6691
  • Language: English
  • DOI: 10.1126/science.abo7027
  • ISSN: 0036-8075; 1095-9203
  • Origination:
  • Footnote:
  • Description: Macrophages are functionally heterogeneous cells essential for apoptotic cell clearance. Apoptotic cells are defined by homogeneous characteristics, ignoring their original cell lineage identity. We found that in an interleukin-4 (IL-4)–enriched environment, the sensing of apoptotic neutrophils by macrophages triggered their tissue remodeling signature. Engulfment of apoptotic hepatocytes promoted a tolerogenic phenotype, whereas phagocytosis of T cells had little effect on IL-4–induced gene expression. In a mouse model of parasite-induced pathology, the transfer of macrophages conditioned with IL-4 and apoptotic neutrophils promoted parasitic egg clearance. Knockout of phagocytic receptors required for the uptake of apoptotic neutrophils and partially T cells, but not hepatocytes, exacerbated helminth infection. These findings suggest that the identity of apoptotic cells may contribute to the development of distinct IL-4–driven immune programs in macrophages.