Bellanti Francesco, Pannone Giuseppe, Tartaglia Nicola, Serviddio Gaetano
Center for Experimental and Regenerative Medicine, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Institute of Anatomical Pathology, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
Front Cell Dev Biol. 2020 May 6;8:295. doi: 10.3389/fcell.2020.00295. eCollection 2020.
The liver commonly self-regenerates by a proliferation of mature cell types. Nevertheless, in case of severe or protracted damage, the organ renewal is mediated by the hepatic progenitor cells (HPCs), adult progenitors capable of differentiating toward the biliary and the hepatocyte lineages. This regeneration process is determined by the formation of a stereotypical niche surrounding the emerging progenitors. The organization of the HPC niche microenvironment is crucial to drive biliary or hepatocyte regeneration. Furthermore, this is the site of a complex immunological activity mediated by several immune and non-immune cells. Indeed, several cytokines produced by monocytes, macrophages and T-lymphocytes may promote the activation of HPCs in the niche. On the other side, HPCs may produce pro-inflammatory cytokines induced by liver inflammation. The inflamed liver is characterized by high generation of reactive oxygen and nitrogen species, which in turn lead to the oxidation of macromolecules and the alteration of signaling pathways. Reactive species and redox signaling are involved in both the immunological and the adult stem cell regeneration processes. It is then conceivable that redox balance may finely regulate the immune response in the HPC niche, modulating the regeneration process and the immune activity of HPCs. In this perspective article, we summarize the current knowledge on the role of reactive species in the regulation of hepatic immunity, suggesting future research directions for the study of redox signaling on the immunomodulatory properties of HPCs.
肝脏通常通过成熟细胞类型的增殖实现自我再生。然而，在严重或长期损伤的情况下，器官更新由肝祖细胞（HPCs）介导，肝祖细胞是能够向胆管和肝细胞谱系分化的成体祖细胞。这种再生过程由围绕新生祖细胞形成的典型生态位决定。HPC生态位微环境的组织对于驱动胆管或肝细胞再生至关重要。此外，这是由几种免疫和非免疫细胞介导的复杂免疫活动发生的场所。实际上，单核细胞、巨噬细胞和T淋巴细胞产生的几种细胞因子可能促进生态位中HPCs的激活。另一方面，HPCs可能产生由肝脏炎症诱导的促炎细胞因子。炎症肝脏的特征是高活性氧和氮物质的产生，这反过来又导致大分子的氧化和信号通路的改变。活性物质和氧化还原信号参与免疫和成人干细胞再生过程。因此可以想象，氧化还原平衡可能精细调节HPC生态位中的免疫反应，调节再生过程和HPCs的免疫活性。在这篇观点文章中，我们总结了关于活性物质在肝脏免疫调节中作用的当前知识，为研究氧化还原信号对HPCs免疫调节特性的影响提出了未来的研究方向。
