Role of immune cells in mediating the effect of phosphatidylcholine (17:0_18:2) on liver cirrhosis

Abstract Liver cirrhosis (LC) is the terminal stage of various chronic liver diseases, with complications of decompensated liver cirrhosis being the primary cause of death. Recent studies have shown that lipid metabolic disorders and chronic inflammatory responses within the liver, leading to fibrosis and inflammation, are associated with the development of liver cirrhosis. This study investigated the causal relationship between phosphatidylcholine (17:0_18:2) (PC) and LC, as well as the mediating role of immune cells. Utilizing summary data from genome-wide association studies (GWAS) and information from the Finnish database, single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for a two-step Mendelian randomization (MR) analysis of gene-predicted LC (including 1266 cases and 407,801 controls). The results indicate a negative causal relationship between genetically predicted PC levels and LC (OR 0.819, 95% CI 0.693–0.967; P = 0.019, IVW method). Immune cells, specifically CD33 on CD33dim HLA DR- (with a mediation effect ratio of 7.027%) and CD33 on Im MDSC (with a mediation effect ratio of 5.763%), play a reverse mediating role in the causal relationship between PC and LC. This study provides a new perspective on the prevention and treatment strategies for liver cirrhosis involving lipid metabolism and immune regulation.