Centre for Liver Research and NIHR BRC, Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom; European Reference Network Centre: Rare Liver, United Kingdom; Queen Elizabeth Hospital, University Hospital of Birmingham NHS Foundation Trust, United Kingdom.
Centre for Liver Research and NIHR BRC, Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom; European Reference Network Centre: Rare Liver, United Kingdom.
Cell Immunol. 2020 Nov;357:104195. doi: 10.1016/j.cellimm.2020.104195. Epub 2020 Aug 14.
The human liver is regarded as a lymphoid organ that contributes to both local and systemic immune response. Intrahepatic immune cells including regulatory T cells (Tregs) reside in the hepatic microenvironment which is enriched with proinflammatory cytokines, chemokines and metabolites. In addition, the hepatic microenvironment has the unique ability to establish and maintain immune tolerance despite the continuous influx of the gut derived microbial products via the portal vein. Regulatory T cells play a crucial role in maintaining the hepatic tolerogenic state; however, the phenotypic stability, function and survival of Tregs in the inflamed liver microenvironment is still poorly understood. Despite this, Tregs immunotherapy remains as an appealing therapeutic option in autoimmune and immune mediated liver diseases. In order to advance cell therapy, it is important for us to further our understanding of the hepatic microenvironment, with the aim of developing ways to modify the hostile, inflamed environment to one which is more favourable. By doing so, T cell stability and function would be enhanced, resulting in improved clinical outcomes.
人类肝脏被认为是一个淋巴器官,有助于局部和全身免疫反应。包括调节性 T 细胞(Tregs)在内的肝内免疫细胞存在于富含促炎细胞因子、趋化因子和代谢物的肝微环境中。此外,尽管门静脉不断有肠道来源的微生物产物涌入,肝微环境仍具有建立和维持免疫耐受的独特能力。调节性 T 细胞在维持肝耐受状态方面发挥着关键作用;然而,Tregs 在炎症性肝微环境中的表型稳定性、功能和存活仍知之甚少。尽管如此,Tregs 免疫疗法仍然是自身免疫和免疫介导的肝病有吸引力的治疗选择。为了推进细胞疗法,我们必须进一步了解肝微环境,目的是找到改变恶劣、炎症环境的方法,使其变得更加有利。这样,T 细胞的稳定性和功能将得到增强,从而改善临床结果。