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- Title
A common framework of monocyte-derived macrophage activation.
- Authors
Sanin, David E.; Ge, Yan; Marinkovic, Emilija; Kabat, Agnieszka M.; Castoldi, Angela; Caputa, George; Grzes, Katarzyna M.; Curtis, Jonathan D.; Thompson, Elizabeth A.; Willenborg, Sebastian; Dichtl, Stefanie; Reinhardt, Susanne; Dahl, Andreas; Pearce, Erika L.; Eming, Sabine A.; Gerbaulet, Alexander; Roers, Axel; Murray, Peter J.; Pearce, Edward J.
- Abstract
Macrophages populate every organ during homeostasis and disease, displaying features of tissue imprinting and heterogeneous activation. The disconnected picture of macrophage biology that has emerged from these observations is a barrier for integration across models or with in vitro macrophage activation paradigms. We set out to contextualize macrophage heterogeneity across mouse tissues and inflammatory conditions, specifically aiming to define a common framework of macrophage activation. We built a predictive model with which we mapped the activation of macrophages across 12 tissues and 25 biological conditions, finding a notable commonality and finite number of transcriptional profiles, in particular among infiltrating macrophages, which we modeled as defined stages along four conserved activation paths. These activation paths include a "phagocytic" regulatory path, an "inflammatory" cytokine-producing path, an "oxidative stress" antimicrobial path, or a "remodeling" extracellular matrix deposition path. We verified this model with adoptive cell transfer experiments and identified transient RELMɑ expression as a feature of monocyte-derived macrophage tissue engraftment. We propose that this integrative approach of macrophage classification allows the establishment of a common predictive framework of monocyte-derived macrophage activation in inflammation and homeostasis. Comment in
- Publication
Science Immunology, 2022, Vol 7, Issue 70, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.abl7482