Zhang Chunye, Sui Yuxiang, Liu Shuai, Yang Ming
Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65212, USA.
School of Life Science, Shanxi Normal University, Linfen 041004, China.
Biomedicines. 2024 Jan 27;12(2):299. doi: 10.3390/biomedicines12020299.
Liver disease-related mortality is a major cause of death worldwide. Hepatic innate and adaptive immune cells play diverse roles in liver homeostasis and disease. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells. MDSCs can be broadly divided into monocytic MDSCs and polymorphonuclear or granulocytic MDSCs, and they functionally interact with both liver parenchymal and nonparenchymal cells, such as hepatocytes and regulatory T cells, to impact liver disease progression. The infiltration and activation of MDSCs in liver disease can be regulated by inflammatory chemokines and cytokines, tumor-associated fibroblasts, epigenetic regulation factors, and gut microbiota during liver injury and cancer. Given the pivotal roles of MDSCs in advanced liver diseases, they can be targeted to treat primary and metastatic liver cancer, liver generation, alcoholic and nonalcoholic liver disease, and autoimmune hepatitis. Currently, several treatments such as the antioxidant and anti-inflammatory agent berberine are under preclinical and clinical investigation to evaluate their therapeutic efficacy on liver disease and their effect on MDSC infiltration and function. Phenotypic alteration of MDSCs in different liver diseases that are in a model-dependent manner and lack special markers for distinct MDSCs are challenges for targeting MDSCs to treat liver disease. Multi-omics study is an option to uncover the features of disease-specific MDSCs and potential gene or protein targets for liver disease treatment. In summary, MDSCs play important roles in the pathogenesis and progression of liver disease by regulating both intrahepatic innate and adaptive immune responses.
肝脏疾病相关的死亡率是全球主要的死亡原因之一。肝脏的固有免疫细胞和适应性免疫细胞在肝脏稳态和疾病中发挥着多种作用。髓系来源的抑制细胞（MDSCs）是一群异质性的未成熟髓系细胞。MDSCs可大致分为单核细胞型MDSCs和多形核或粒细胞型MDSCs，它们在功能上与肝脏实质细胞和非实质细胞相互作用，如肝细胞和调节性T细胞，从而影响肝脏疾病的进展。在肝脏损伤和癌症过程中，炎症趋化因子、细胞因子、肿瘤相关成纤维细胞、表观遗传调控因子和肠道微生物群可调节MDSCs在肝脏疾病中的浸润和激活。鉴于MDSCs在晚期肝脏疾病中的关键作用，可将其作为靶点来治疗原发性和转移性肝癌、肝生成、酒精性和非酒精性肝病以及自身免疫性肝炎。目前，诸如抗氧化剂和抗炎剂黄连素等几种治疗方法正在进行临床前和临床研究，以评估它们对肝脏疾病的治疗效果以及对MDSC浸润和功能的影响。不同肝脏疾病中MDSCs的表型改变依赖于模型，且缺乏针对不同MDSCs的特殊标志物，这是将MDSCs作为靶点治疗肝脏疾病所面临的挑战。多组学研究是揭示疾病特异性MDSCs特征以及肝脏疾病治疗潜在基因或蛋白质靶点的一种选择。总之，MDSCs通过调节肝内固有免疫和适应性免疫反应，在肝脏疾病的发病机制和进展中发挥重要作用。
