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

Imke Liebold; Amirah Al Jawazneh; Christian Casar; Clarissa Lanzloth; Stephanie Leyk; Madeleine Hamley; Milagros N. Wong; Dominik Kylies; Stefanie K. Gräfe; Ilka Edenhofer; Irene Aranda-Pardos; Marie Kriwet; Helmuth Haas; Jenny Krause; Alexandros Hadjilaou; Andra B. Schromm; Ulricke Richardt; Petra Eggert; Dennis Tappe; Sören A. Weidemann; Sourav Ghosh; Christian F. Krebs; Noelia A-Gonzalez; Anna Worthmann; Ansgar W. Lohse; Samuel Huber; Carla V. Rothlin; Victor G. Puelles; Thomas Jacobs; Nicola Gagliani; Lidia Bosurgi

doi:10.1126/science.abo7027

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

Imke Liebold, Amirah Al Jawazneh, Christian Casar, Clarissa Lanzloth, Stephanie Leyk, Madeleine Hamley, Milagros N. Wong, Dominik Kylies, Stefanie K. Gräfe, Ilka Edenhofer, Irene Aranda-Pardos, Marie Kriwet, Helmuth Haas, Jenny Krause, Alexandros Hadjilaou, Andra B. Schromm, Ulricke Richardt, Petra Eggert, Dennis Tappe, Sören A. WeidemannSourav Ghosh, Christian F. Krebs, Noelia A-Gonzalez, Anna Worthmann, Ansgar W. Lohse, Samuel Huber, Carla V. Rothlin, Victor G. Puelles, Thomas Jacobs, Nicola Gagliani^*, Lidia Bosurgi^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

14 Citations (Scopus)

Abstract

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.

Original language	English
Article number	eabo7027
Journal	Science
Volume	384
Issue	6691
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.abo7027
Publication status	Published - 5 Apr 2024

Keywords

Animals
Apoptosis/immunology
Disease Models, Animal
Hepatocytes/immunology
Interleukin-4/genetics
Macrophages/immunology
Mice
Mice, Knockout
Neutrophils/immunology
Phagocytosis/immunology
Schistosomiasis mansoni/genetics

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10.1126/science.abo7027

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Liebold, I., Jawazneh, A. A., Casar, C., Lanzloth, C., Leyk, S., Hamley, M., Wong, M. N., Kylies, D., Gräfe, S. K., Edenhofer, I., Aranda-Pardos, I., Kriwet, M., Haas, H., Krause, J., Hadjilaou, A., Schromm, A. B., Richardt, U., Eggert, P., Tappe, D., ... Bosurgi, L. (2024). Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages. Science, 384(6691), Article eabo7027. https://doi.org/10.1126/science.abo7027

@article{338ebf22bb894f8f807da485a93fa8cd,

title = "Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages",

abstract = "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.",

keywords = "Animals, Apoptosis/immunology, Disease Models, Animal, Hepatocytes/immunology, Interleukin-4/genetics, Macrophages/immunology, Mice, Mice, Knockout, Neutrophils/immunology, Phagocytosis/immunology, Schistosomiasis mansoni/genetics",

author = "Imke Liebold and Jawazneh, {Amirah Al} and Christian Casar and Clarissa Lanzloth and Stephanie Leyk and Madeleine Hamley and Wong, {Milagros N.} and Dominik Kylies and Gr{\"a}fe, {Stefanie K.} and Ilka Edenhofer and Irene Aranda-Pardos and Marie Kriwet and Helmuth Haas and Jenny Krause and Alexandros Hadjilaou and Schromm, {Andra B.} and Ulricke Richardt and Petra Eggert and Dennis Tappe and Weidemann, {S{\"o}ren A.} and Sourav Ghosh and Krebs, {Christian F.} and Noelia A-Gonzalez and Anna Worthmann and Lohse, {Ansgar W.} and Samuel Huber and Rothlin, {Carla V.} and Puelles, {Victor G.} and Thomas Jacobs and Nicola Gagliani and Lidia Bosurgi",

year = "2024",

month = apr,

day = "5",

doi = "10.1126/science.abo7027",

language = "English",

volume = "384",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6691",

}

Liebold, I, Jawazneh, AA, Casar, C, Lanzloth, C, Leyk, S, Hamley, M, Wong, MN, Kylies, D, Gräfe, SK, Edenhofer, I, Aranda-Pardos, I, Kriwet, M, Haas, H, Krause, J, Hadjilaou, A, Schromm, AB, Richardt, U, Eggert, P, Tappe, D, Weidemann, SA, Ghosh, S, Krebs, CF, A-Gonzalez, N, Worthmann, A, Lohse, AW, Huber, S, Rothlin, CV, Puelles, VG, Jacobs, T, Gagliani, N & Bosurgi, L 2024, 'Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages', Science, vol. 384, no. 6691, eabo7027. https://doi.org/10.1126/science.abo7027

TY - JOUR

T1 - Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages

AU - Liebold, Imke

AU - Jawazneh, Amirah Al

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 - Kriwet, Marie

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

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 - Apoptosis/immunology

KW - Disease Models, Animal

KW - Hepatocytes/immunology

KW - Interleukin-4/genetics

KW - Macrophages/immunology

KW - Mice

KW - Mice, Knockout

KW - Neutrophils/immunology

KW - Phagocytosis/immunology

KW - Schistosomiasis mansoni/genetics

UR - http://www.scopus.com/inward/record.url?scp=85189910063&partnerID=8YFLogxK

U2 - 10.1126/science.abo7027

DO - 10.1126/science.abo7027

M3 - Journal article

C2 - 38574142

AN - SCOPUS:85189910063

SN - 0036-8075

VL - 384

JO - Science

JF - Science

IS - 6691

M1 - eabo7027

ER -

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

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