1. The cross-talk between macrophages and the microenviroment controls tissue regeneration.
The cross-talk between macrophages and the microenviroment controls tissue regeneration. scRNAseq enables the identification of key surface markers of macrophages in both proregenerative and profibrotic environments, allowing subsequent characterization of their frequency and function over time. Microenvironmental cues favor macrophage polarization into the regenerative clusters R1 (CD9+CD301b+MHCIIhi) and R2 (CD9−CD301b+CD206+) or into the fibrotic clusters F1 (CD9− CD301b−MHCIIhi) and F2 (CD9hiCD301b−MHCII−IL36γ+). Although both R1 and F1 are marked by proinflammatory responses, their magnitude and composition differ and lead to opposing outcomes. R1 and R2 assist tissue repair by actively engaging and coordinating immune cells in a coinciding effort toward regeneration. R1 mobilizes and instructs cells through chemokine expression and antigen presentation, and R2 coordinates a type 2 response through Il-4 and Ccl24 expression and exhibits phagocytic activity. Conversely, F1 and F2 drive FBR. F1 directs the exacerbated expression of interferon-related cytokines, and F2 favors fibrosis by feeding and thriving in a microenvironment marked by type 17 immune responses. ECM, extracellular matrix; PCL, polycaprolactone.
Catia T. Perciani, and Sonya A. MacParland Sci. Immunol. 2019;4:eaaz0749
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