Overexpression of fibrinogen-like protein 2 alleviates acute rejection in rat models of liver transplantation

Background: The role of cluster of differentiation (CD)8+ regulatory T cells (Tregs) has previously been elucidated in tolerance models. Fibrinogen-like protein 2 (FGL2), that is secreted by Treg cells, which exhibited immunosuppressive functions, may alleviate acute rejection (AR). However, the precise role of CD8+ Tregs and FGL2 in the AR of rat liver transplantation remains unknown. Our previous study found that CD8+CD45RClow Tregs played crucial roles in maintaining immune tolerance. Here, we elucidated the role of CD8+ CD45RClowTreg and FGL2 in AR of rat liver transplantation. Methods: A rat non-materialized AR of liver transplantation model was established using donors infected with no-load adeno-associated virus and adeno-associated virus expressing FGL2. Results: There was an accumulation of tolerogenic CD8+CD45RClow in allografts compared with blank groups. Moreover, the proportion of CD8+CD45RClow Tregs was increased with longer survival time. Furthermore, we detected higher levels of FGL2 in the allografts infected with AAV-FGL2 in rats with AR of liver transplantation. We found that FGL2 could alleviate AR, and the survival time was prolonged in the recipients of donors infected with AAV-FGL2. Conclusions: Our data suggest that CD8+CD45RClow Tregs was accumulated in allografts. The presence of FGL2 alleviated AR and prolonged survival time in the AR of liver transplantation rat model, suggesting that FGL2 and CD8+CD45RClow Tregs may serves as novel therapeutic targets for AR in liver transplantation.

Automated summary

The study revealed the significant role of CD8+ regulatory T cells (Tregs) and FGl2 in acute rejection (AR) of rat liver transplantation. Findings showed the accumulation of CD8+CD45RClow Tregs in allografts, the alleviation of AR with the presence of FGL2, and the prolongation of survival time in recipients, suggesting FGL2 and CD8+CD45RClow Tregs as potential therapeutic targets for AR in liver transplantation.