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 RELMα 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.
Original language | English (US) |
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Article number | abl7482 |
Journal | Science Immunology |
Volume | 7 |
Issue number | 70 |
DOIs | |
State | Published - Apr 2022 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology