Soluble fibrinogen‐like protein 2 ameliorates acute rejection of liver transplantation in rat via inducing Kupffer cells M2 polarization

Abstract Soluble fibrinogen‐like protein 2 ( sFGL 2) could ameliorate acute rejection ( AR ) in rat cardiac transplantation. However, the role of sFGL 2 in AR of liver transplantation has not been addressed. In this study, we found that FGL 2 was upregulated in rat orthotropic liver transplantation ( OLT ) models of tolerance and positive correlation with the frequency of M2 Kupffer cells ( KC s). Gain‐of‐function experiments in vitro showed that sFGL 2 promoted the secretion of anti‐inflammatory cytokines ( IL ‐10, TGF ‐β) and the expression of CD 206, and inhibited the activities of STAT 1 and NF ‐κB signaling pathway. Consistently, in vivo assays showed that adeno‐associated virus‐mediated FGL 2 ( AAV ‐ FGL 2) transfer to recipients could ameliorate AR of rat OLT and induce KC s M2 polarization in allografts. Notably, we found that the recipients receiving transferred KC s from AAV ‐ FGL 2‐treated allograft showed alleviated AR . Taken together, we revealed that sFGL 2 ameliorated AR by inducing KC s M2 polarization.