Science (New York, N.Y.) · 2024
Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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, Lohse Ansgar W, Huber Samuel, Rothlin Carla V, Puelles Victor G, Jacobs Thomas, Gagliani Nicola, Bosurgi Lidia
Аннотация
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.