There is increasing awareness of the immunologic roles of liver mononuclear populations, including myeloid‐derived suppressor cells (MDSCs). We took advantage of a large well‐defined cohort of 148 patients with liver inflammation and 45 healthy controls to focus on the qualitative and quantitative characteristics of MDSCs. We investigated the frequency, phenotype, and functional capacities of MDSCs by using peripheral blood MDSCs in a cohort of 55 patients with primary biliary cholangitis (PBC), 40 with autoimmune hepatitis, 39 with chronic hepatitis B, 14 with nonalcoholic fatty liver disease, and 45 healthy controls. This was followed by a liver‐targeted determination in 27 patients with PBC, 27 with autoimmune hepatitis, 20 with chronic hepatitis B, 14 with nonalcoholic fatty liver disease, and 6 controls. We then focused on mechanisms of this expansion with PBC as an example, using both ursodeoxycholic acid‐naive and treated patients. HLA‐DR−/lowCD33+CD11b+CD14+CD15− monocytic MDSCs were elevated in diseases characterized by liver inflammation compared to healthy controls. Using PBC as a focus, there was a significant correlation between levels of circulating MDSCs and disease‐related biochemical markers (alkaline phosphatase, total bilirubin). We found higher amounts of MDSCs in patients with PBC who were responsive to ursodeoxycholic acid. MDSCs from PBC were found to manifest a potent immunosuppressive function. There was a significant correlation in the accumulation of hepatic MDSCs in the inflamed lesions of PBC with histologic changes, such as fibrosis. We also found that cysteine‐rich protein 61 (CCN1), a highly expressed protein in impaired cholangiocytes and hepatocytes, contributes to MDSC expansion and MDSC inducible nitric oxide synthase‐associated immune suppression. Conclusion: CCN1 modulates expansion and a suppressive function of MDSCs. Our data highlight the potential functions of CCN1 on MDSCs and suggest therapeutic implications in inflammatory liver diseases. (Hepatology HEPATOLOGY 2018;67:232‐246).

中文翻译：

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髓源性抑制细胞在肝脏炎症中的功能特征 CCNI 调节

人们越来越意识到肝脏单核细胞群的免疫作用，包括骨髓源性抑制细胞 (MDSCs)。我们利用由 148 名肝脏炎症患者和 45 名健康对照者组成的大型明确队列来关注 MDSCs 的定性和定量特征。我们通过使用外周血 MDSCs 在 55 名原发性胆汁性胆管炎 (PBC) 患者、40 名自身免疫性肝炎患者、39 名慢性乙型肝炎患者、14 名非酒精性脂肪肝患者以及45 个健康对照。随后对 27 名 PBC 患者、27 名自身免疫性肝炎患者、20 名慢性乙型肝炎患者、14 名非酒精性脂肪肝患者和 6 名对照者进行了肝脏靶向测定。然后，我们以 PBC 为例，使用熊去氧胆酸初治患者和接受治疗的患者关注这种扩增的机制。与健康对照相比，HLA-DR-/lowCD33+CD11b+CD14+CD15-单核细胞 MDSC 在以肝脏炎症为特征的疾病中升高。以 PBC 为焦点，循环 MDSCs 水平与疾病相关生化标志物（碱性磷酸酶、总胆红素）之间存在显着相关性。我们发现对熊去氧胆酸有反应的 PBC 患者的 MDSC 量更高。发现来自 PBC 的 MDSC 表现出有效的免疫抑制功能。PBC 炎症病变中肝脏 MDSC 的积累与组织学变化（如纤维化）有显着相关性。我们还发现富含半胱氨酸的蛋白质 61 (CCN1)，在受损的胆管细胞和肝细胞中高表达的蛋白质，有助于 MDSC 扩增和 MDSC 诱导型一氧化氮合酶相关免疫抑制。结论：CCN1 调节 MDSCs 的扩张和抑制功能。我们的数据突出了 CCN1 对 MDSC 的潜在功能，并提示了炎症性肝病的治疗意义。（肝病学 HEPATOLOGY 2018；67:232-246）。