Decreased Foxp3 and function of Tregs caused immune imbalance and liver injury in patients with autoimmune liver diseases post-liver transplantation
Decreased Foxp3 and function of Tregs caused immune imbalance and liver injury in patients with autoimmune liver diseases post-liver transplantation
复制标题
Foxp3和Tregs功能下降导致自身免疫性肝病患者肝移植后免疫失衡和肝损伤
DOI：
10.21037/atm.2020.03.203
复制
发表时间：
2020-04-01
影响因子：
--
通讯作者：
Wang, Ke
中科院分区：
文献类型：
--
作者：
Liu, Zheng;Gu, Jian;Wang, Ke
背景：自身免疫性肝病（AILD）是一种自身免疫性疾病，可能导致终末期肝衰竭并需要肝移植。调节性T细胞（Tregs）在维持免疫稳态中发挥着不可替代的作用。方法：本研究对AILD患者移植后与乙型肝炎病毒（HBV）感染肝衰竭患者移植后的免疫平衡和移植物功能进行比较分析。分析两组的免疫细胞表型。我们对 CD4+CD25+CD127-Tregs 进行体外和体内分类，并进行 TSDR 甲基化状态检测，以探索进一步可能的机制。 结果：我们的数据显示，与 HBV 诱导的肝衰竭患者相比，AILD 肝移植患者的预后较差，移植功能严重。免疫细胞表型分析显示，与移植后的 HBV 患者相比，AILD 患者中可以检测到更多的 Tregs。我们对体内 CD4+CD25+CD127-Tregs 进行了分类，结果表明 Tregs 在体外和体内均表现出功能下降。机制研究还证明，调节Foxp3中STAT1和STAT3的磷酸化水平以及Foxp3中TSDR的甲基化水平可能部分导致Tregs的功能丧失。结论：这些结果提示Foxp3表达的丧失和Tregs的抑制功能可能是导致AILD后肝移植患者移植物丢失的关键因素。
Background: Autoimmune liver diseases (AILD) is a type of autoimmune disease which may cause endstage 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.