FPR1 in myeloid cells is a crucial factor associated with the inflammatory response; however, whether FPR1 signaling affects MASH development remains largely unknown.In this study, we demonstrated that Fpr1 deficiency in myeloid cells and administration of an FPR1 inhibitor robustly limit MASH-related fibrosis, which is closely related with the downregulation of proinflammatory S100A4 and S100A11.In addition, neutrophil-derived ANXA1 elevates the expression of S100A4 and S100A11 in neutrophils and macrophages by activating FPR1 signaling, suggesting that the ANXA1-FPR1-S100A4/A11 axis plays an important role in worsening MASH. Highlights: Myeloid cell-specific Fpr1 deficient mice are more resistant to MASH. Administration of FPR1 inhibitor robustly ameliorates MASH. The ANXA1-FPR1 axis elevates the expression of proinflammatory S100A4 and S100A11.
Yang et al. (Wed,) studied this question.