Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation

Tobias Weinberger (1, 2) , Dena Esfandyari (2, 3) , Denise Messerer (1, 2) , Gulce Percin (4) , Christian Schleifer (1, 2) , Raffael Thaler (1, 2) , Lulu Liu (1, 2) , Christopher Stremmel (1, 2) , Vanessa Schneider (1, 2) , Ronald Vagnozzi (5) , Jennifer Schwanenkamp (5) , Maximilian Fischer (1, 2) , Katrin Busch (6) , Kay Klapproth (6) , Hellen Ishikawa-Ankerhold (1, 2) , Lukas Klösges (1, 2) , Anna Titova (1, 2) , Jeffery Molkentin (5) , Yasuhiro Kobayashi (7) , Stefan Engelhardt (2, 3) , Steffen Massberg (1, 2) , Claudia Waskow (4, 8) , Elisa Gomez Perdiguero (9) , Christian Schulz (1, 2, 10)

1 Klinikum der Universitat Munchen
2 DZHK site Munich Heart Alliance
3 Institute of pharmacology and toxicology
4 FLI - Leibniz Institute on Aging - Fritz Lipmann Institute
5 Cincinnati Children's Hospital Medical Center
6 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
7 Institute for Oral Science, Matsumoto Dental University
8 Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany]
9 Macrophages et Cellules endothéliales / Macrophages and Endothelial Cells
10 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München

Abstract Arterial macrophages have different developmental origins, but the association of macrophage ontogeny with their phenotypes and functions in adulthood is still unclear. Here, we combine macrophage fate-mapping analysis with single-cell RNA sequencing to establish their cellular identity during homeostasis, and in response to angiotensin-II (AngII)-induced arterial inflammation. Yolk sac erythro-myeloid progenitors (EMP) contribute substantially to adventitial macrophages and give rise to a defined cluster of resident immune cells with homeostatic functions that is stable in adult mice, but declines in numbers during ageing and is not replenished by bone marrow (BM)-derived macrophages. In response to AngII inflammation, increase in adventitial macrophages is driven by recruitment of BM monocytes, while EMP-derived macrophages proliferate locally and provide a distinct transcriptional response that is linked to tissue regeneration. Our findings thus contribute to the understanding of macrophage heterogeneity, and associate macrophage ontogeny with distinct functions in health and disease.

Domaines: Immunologie; Cardiologie et système cardiovasculaire

Tobias Weinberger, Dena Esfandyari, Denise Messerer, Gulce Percin, Christian Schleifer, et al.. Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation. Nature Communications, 2020, 11 (1), ⟨10.1038/s41467-020-18287-x⟩. ⟨hal-03263906⟩