College of Medical and Dental Sciences, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Front Immunol. 2021 Apr 19;12:662134. doi: 10.3389/fimmu.2021.662134. eCollection 2021.
Persistent liver inflammation can lead to cirrhosis, which associates with significant morbidity and mortality worldwide. There are no curative treatments beyond transplantation, followed by long-term immunosuppression. The global burden of end stage liver disease has been increasing and there is a shortage of donor organs, therefore new therapies are desperately needed. Harnessing the power of the immune system has shown promise in certain autoimmunity and cancer settings. In the context of the liver, regulatory T cell (Treg) therapies are in development. The hypothesis is that these specialized lymphocytes that dampen inflammation may reduce liver injury in patients with chronic, progressive diseases, and promote transplant tolerance. Various strategies including intrinsic and extracorporeal expansion of Treg cells, aim to increase their abundance to suppress immune responses. We recently discovered that hepatocytes engulf and delete Treg cells by enclysis. Herein, we propose that inhibition of enclysis may potentiate existing regulatory T cell therapeutic approaches in patients with autoimmune liver diseases and in patients receiving a transplant. Moreover, in settings where the abundance of Treg cells could hinder beneficial immunity, such us in chronic viral infection or liver cancer, enhancement of enclysis could result in transient, localized reduction of Treg cell numbers and tip the balance towards antiviral and anti-tumor immunity. We describe enclysis as is a natural process of liver immune regulation that lends itself to therapeutic targeting, particularly in combination with current Treg cell approaches.
持续的肝脏炎症可导致肝硬化，这在全球范围内与显著的发病率和死亡率相关。除了移植之外，没有治愈方法，随后需要长期免疫抑制。终末期肝病的全球负担一直在增加，而供体器官短缺，因此迫切需要新的治疗方法。利用免疫系统的力量在某些自身免疫和癌症环境中显示出了希望。在肝脏的背景下，调节性 T 细胞（Treg）治疗正在开发中。其假设是，这些专门的抑制炎症的淋巴细胞可能会减轻慢性进行性疾病患者的肝损伤，并促进移植耐受。各种策略，包括 Treg 细胞的内在和体外扩增，旨在增加其丰度以抑制免疫反应。我们最近发现肝细胞通过吞噬作用来吞噬和消除 Treg 细胞。在此，我们提出抑制吞噬作用可能会增强自身免疫性肝病患者和接受移植患者的现有调节性 T 细胞治疗方法。此外，在 Treg 细胞丰度可能会阻碍有益免疫的情况下，例如慢性病毒感染或肝癌，增强吞噬作用可能会导致 Treg 细胞数量的短暂、局部减少，并使抗病毒和抗肿瘤免疫倾向于有利的方向。我们将吞噬作用描述为肝脏免疫调节的自然过程，特别适合于与当前的 Treg 细胞方法联合进行治疗靶向。
