Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages
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Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages. / 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 (Autor/-in intern machen); 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; Lohse, Ansgar W; Huber, Samuel; Rothlin, Carla V; Puelles, Victor G; Jacobs, Thomas; Gagliani, Nicola; Bosurgi, Lidia.
in: SCIENCE, Jahrgang 384, Nr. 6691, 05.04.2024, S. eabo7027.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung
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TY - JOUR
T1 - Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages
AU - Liebold, Imke
AU - Al Jawazneh, Amirah
AU - Casar, Christian
AU - Lanzloth, Clarissa
AU - Leyk, Stephanie
AU - Hamley, Madeleine
AU - Wong, Milagros N
AU - Kylies, Dominik
AU - Gräfe, Stefanie K
AU - Edenhofer, Ilka
AU - Aranda-Pardos, Irene
AU - Haas, Helmuth
AU - Krause, Jenny
AU - Hadjilaou, Alexandros
AU - Schromm, Andra B
AU - Richardt, Ulricke
AU - Eggert, Petra
AU - Tappe, Dennis
AU - Weidemann, Sören A
AU - Ghosh, Sourav
AU - Krebs, Christian F
AU - A-Gonzalez, Noelia
AU - Worthmann, Anna
AU - Lohse, Ansgar W
AU - Huber, Samuel
AU - Rothlin, Carla V
AU - Puelles, Victor G
AU - Jacobs, Thomas
AU - Gagliani, Nicola
AU - Bosurgi, Lidia
A2 - Kriwet, Marie
PY - 2024/4/5
Y1 - 2024/4/5
N2 - 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.
AB - 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.
KW - Animals
KW - Mice
KW - Apoptosis/immunology
KW - Hepatocytes/immunology
KW - Interleukin-4/genetics
KW - Macrophages/immunology
KW - Mice, Knockout
KW - Neutrophils/immunology
KW - Phagocytosis/immunology
KW - Schistosomiasis mansoni/genetics
KW - Disease Models, Animal
U2 - 10.1126/science.abo7027
DO - 10.1126/science.abo7027
M3 - SCORING: Journal article
C2 - 38574142
VL - 384
SP - eabo7027
JO - SCIENCE
JF - SCIENCE
SN - 0036-8075
IS - 6691
ER -