Transcriptomic analysis of Kupffer cells in patients with cirrhosis

Background and aims: Patients with decompensated cirrhosis present serious infections of bacterial origin. During homeostasis, resident macrophages from the liver or Kupffer cells (KCS) play a key role in the phagocytosis of circulating bacteria. The objective of this study was to characterize the transcripomic and functional profile of KCs in liver cirrhosis and its relationship with the risk of infections. Methods: KCs were isolated from livers of patients with cirrhosis (n = 4) and controls (n = 5) and the profile was determined by RNA sequencing. The phenotype and altered molecular pathways of the isolated KCS were analyzed through GSEA . Results: The expression profile of KCs is specific and different depending on whether they reside in a cirrhotic or control liver. The GO analysis revealed that the pathways differentially expressed in KCs isolated from cirrhotic liver are implicated in the immune response. The GSEA showed that KCs isolated from patients with cirrhosis present a greater overexpression of M1 markers with respect to M2 (normalized enrichment score, NES: 1.68, p <0.01 vs. NES: 0.8, p <0.01). Conclusion: The KCS of patients with cirrhosis have a unique and distinct gene expression profile characterized by up-regulation of M1 markers. Overall design: KC were isolatrd from decompensated cirrhosis that underwent liver transplantation (n=4) and a control group of patients with liver tumours (except hepatocellular carcinoma) and without underlying liver disease (n=5). Morever, whole liver tissue from the same patients were aso sequenced.