Decreased Foxp3 and function of Tregs caused immune imbalance and liver injury in patients with autoimmune liver diseases post-liver transplantation

BACKGROUND: Autoimmune liver diseases (AILD) is a type of autoimmune disease which may cause end-stage liver failure and require liver transplantation. Regulatory T cells (Tregs) play an irreplaceable role in maintaining immunological homeostasis. METHODS: In this study, we made a comparative analysis of the immune balance and graft function between AILD patients’ post-transplantation and the patients who have had liver failure with hepatitis B virus (HBV) infection post-transplantation. Immune cell phenotype of two groups were analyzed. We sorted CD4+CD25+CD127-Tregs both in vitro and vivo and did TSDR methylation status assay to explore further possible mechanisms. RESULTS: Our data showed that there is a worse prognosis with severe graft function in liver transplant patients with AILD compared to patients with HBV-induced liver failure. Immune cell phenotype analysis showed that more Tregs could be detected in AILD patients compared with HBV patients’ post-transplantation. We sorted CD4+CD25+CD127-Tregs in vivo and showed that Tregs presented decreased function both in vitro and vivo. Mechanism study also proved that modulation of the phosphorylation level of STAT1 and STAT3 as well as the methylation level of TSDR in Foxp3 might partially result in the function loss of Tregs. CONCLUSIONS: These results suggest that loss of Foxp3 expression and suppressive function of Tregs may be the critical factor that causes graft loss for liver transplant patients after AILD.