CD4+CD25+ Foxp3+ Treg protect against T cell‐mediated fumilant hepatitis in a TGF‐β‐dependent manner in mice

The intrahepatic immune environment is associated with the induction of tolerance. Regulatory T cells (Tregs) may play a role in tolerance in the liver. In this study, we examined the role of hepatic CD4+CD25+ Tregs in the liver injury by using Concanavalin A (Con A)‐induced hepatitis model. We found that increased number of Foxp3+ Tregs was observed in the liver but not in the spleen in mice intravenously injected with sublethal dose of Con A. Moreover, the expression levels of Foxp3, cytotoxic T lymphocyte associated antigen‐4 (CTLA‐4), glucocorticoid‐induced tumor necrosis factor receptor (GITR), as well as, the frequency and expression level of CD103 of Tregs were increased after Con A injection and significantly higher in liver than in spleen. Depleting CD25+ cells aggravated liver injury and adoptively transferring of CD25+ cells reduced liver injury, these indicate a functional role of Tregs in Con A‐induced hepatitis. Finally, TGF‐β receptor II dominant‐negative (dnTGF‐βRII) mice, which T cells express a dominant negative form of TGF‐βRII and therefore cannot response to TGF‐β, had a higher mortality rate and severer liver injury than normal mice injected with the same dose of Con A. In conclusion, CD4+CD25+ Tregs are important in the protection against liver injury via a TGF‐β‐dependent mechanism.