Abstract
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.
Highlights
With the prevention and control of hepatitis B and the country's rapid economic growth, alcoholic liver disease (ALD) represents a greater proportion of liver diseases in China.[1]
We found that the Granulocytic myeloid‐derived suppressor cell (gMDSC) population was increased in ALD patients and was closely associated with disease severity
We provide evidence for the enhanced suppressive function of gMDSCs in ALD
Summary
With the prevention and control of hepatitis B and the country's rapid economic growth, alcoholic liver disease (ALD) represents a greater proportion of liver diseases in China.[1]. Few studies have sought to determine the protective role of the immune response during ALD progression. The absence of cysteine prevents the production of proteins related to T cell activation.[10]. Cytokines such as granulocyte colony stimulating factor and granulocyte‐macrophage colony stimulating factor are increased under pathological conditions, effectively stimulating the proliferation of MDSCs. different MDSC subsets with various phenotypic and functional features are classified as CD33+CD11bhighCD14+HLA−DR−CD15− monocytic MDSCs (mMDSCs) and CD33+CD11bhighHLA−DR−CD14−CD15+ granulocytic MDSCs (gMDSCs).[11]. Accumulating evidence indicates that gMDSCs produce high levels of arginase I, IL‐10 and transforming growth factor‐β (TGF‐β) 7,12–14 and play a vital role in regulating the immune environment. We characterized gMDSCs in two groups of patients to determine the correlation between gMDSCs and the severity of ALD and found that the gMDSC population was increased in ALD patients and closely associated with disease progression
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