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Spp1+ Macrophages Trained by Platelets Activate Myofibroblasts in Fibrosis in a Cxcl4-dependent way

Suzanne Jones

Independent of the initial insult, fibrosis is a common final stage of chronic organ injury that destroys tissue architecture and results in organ failure. Here, we identify a profibrotic macrophage population that increases following organ injury and is characterised by the expression of Spp1, Fn1, and Arg1. We determine the chemokine (C-X-C motif) ligand 4 (CXCL4) to be one of the top elevated genes during profibrotic Spp1 macrophage development using an unbiased method. Loss of Cxcl4 prevents profibrotic Spp1 macrophage development and lessens fibrosis following both heart and kidney injury, according to in vitro and in vivo investigations.