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

• 成果类型: Article
• 署名作者: Liebold, Imke; Al Jawazneh, Amirah; Casar, Christian; Lanzloth, Clarissa; Leyk, Stephanie; Hamley, Madeleine; Wong, Milagros N.; Kylies, Dominik; Graefe, 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, Soeren A.; Ghosh, Sourav; Krebs, Christian F.; A-Gonzalez, Noelia; Worthmann, Anna; Lohse, Ansgar W.; Huber, Samuel; Rothlin, Carla V.; Puelles, Victor G.; Jacobs, Thomas; Gagliani, Nicola; Bosurgi, Lidia
• 署名单位: University of Hamburg; University Medical Center Hamburg-Eppendorf; Leibniz Association; Bernhard Nocht Institut fur Tropenmedizin; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Hamburg; University Medical Center Hamburg-Eppendorf; Aarhus University; Aarhus University; University of Munster; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Hamburg; University Medical Center Hamburg-Eppendorf; Leibniz Association; Forschungszentrum Borstel; Leibniz Association; Bernhard Nocht Institut fur Tropenmedizin; University of Hamburg; University Medical Center Hamburg-Eppendorf; Yale University; Yale University; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Hamburg; University Medical Center Hamburg-Eppendorf; Yale University; University of Hamburg; University Medical Center Hamburg-Eppendorf
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12042
• DOI: 10.1126/science.abo7027
• 发表日期: 2024-04-05
• 关键词: tissue; neutrophils; activation; receptor; phagocytosis; fibrosis; phosphatidylserine; inflammation; RECOGNITION; monocytes

摘要

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.