| First Author | Sanin DE | Year | 2022 |
| Journal | Sci Immunol | Volume | 7 |
| Issue | 70 | Pages | eabl7482 |
| PubMed ID | 35427180 | Mgi Jnum | J:333993 |
| Mgi Id | MGI:7430874 | Doi | 10.1126/sciimmunol.abl7482 |
| Citation | Sanin DE, et al. (2022) A common framework of monocyte-derived macrophage activation. Sci Immunol 7(70):eabl7482 |
| abstractText | 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 RELMa 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. |
