Granulocytic myeloid-derived suppressor cell population increases with the severity of alcoholic liver disease

Alcoholic liver disease (ALD) is a progressive liver disease that can cause a series of complications, including cirrhosis, liver failure and hepatocellular carcinoma. Granulocytic myeloid-derived suppressor cell (gMDSC) populations have been observed to expand in various liver diseases and to inhibit innate and adaptive immunity in patients with liver disease. However, the characteristics of gMDSCs in patients with ALD have not been studied. We studied 24 healthy controls (HCs) and 107 patients with ALD and found an accumulation of gMDSCs in the peripheral blood of patients with alcoholic liver cirrhosis (ALC). Furthermore, ALC patients with a poor prognosis displayed a significant increase in peripheral gMDSCs and showed an increased capacity for arginase I production compared to HCs. In contrast, plasma arginase I levels in ALC patients were negatively correlated with total bilirubin and international normalized ratio, two key parameters of liver damage. Importantly, gMDSCs accumulated in the livers of ALC patients, and the frequency of liver gMDSCs significantly correlated with that of peripheral gMDSCs. In addition, gMDSC enrichment in vitro significantly inhibited the function of natural killer (NK) cells, perhaps preventing the NK-induced apoptosis of hepatic stellate cells. In summary, increased peripheral and intrahepatic gMDSC populations are present in patients with ALC and may contribute to enhancing the severity of liver cirrhosis.

酒精性肝病（ALD）是一种进行性肝病，可导致一系列并发症，包括肝硬化、肝衰竭和肝细胞癌。已观察到粒细胞髓系来源的抑制细胞（gMDSC）群在多种肝病中扩增，并抑制肝病患者的固有免疫和适应性免疫。然而，酒精性肝病患者中gMDSC的特征尚未得到研究。我们研究了24名健康对照者（HCs）和107名酒精性肝病患者，发现酒精性肝硬化（ALC）患者外周血中gMDSC积聚。此外，预后不良的ALC患者外周gMDSC显著增加，并且与健康对照者相比，精氨酸酶I产生能力增强。相反，ALC患者血浆精氨酸酶I水平与总胆红素和国际标准化比值（肝脏损伤的两个关键参数）呈负相关。重要的是，gMDSC在ALC患者肝脏中积聚，肝脏gMDSC的频率与外周gMDSC的频率显著相关。此外，体外gMDSC富集显著抑制自然杀伤（NK）细胞的功能，可能阻止NK诱导的肝星状细胞凋亡。总之，ALC患者存在外周和肝内gMDSC群增加，可能有助于加重肝硬化的严重程度。