IL-6-mediated inhibition of NK cell effector functions by monocytes/macrophages via the PD-L1/PD-1 axis in acute-on-chronic liver failure
10.13315/j.cnki.cjcep.2025.10.011
- VernacularTitle:慢加急性肝衰竭中IL-6介导单核/巨噬细胞通过PD-L1-PD-1轴抑制NK细胞效应功能的研究
- Author:
Mengtao GONG
1
;
Yungui WANG
;
Xiangshan FAN
;
Meijuan ZHENG
Author Information
1. 安徽医科大学第一附属医院检验科,合肥 230022
- Publication Type:Journal Article
- Keywords:
acute-on-chronic liver failure;
monocytes;
macrophages;
NK cells;
IL-6;
PD-L1/PD-1 axis
- From:
Chinese Journal of Clinical and Experimental Pathology
2025;41(10):1329-1337
- CountryChina
- Language:Chinese
-
Abstract:
Purpose To investigate how IL-6-mediated monocytes/macrophages suppress the effector function of natural killer(NK)cells through the PD-L1/PD-1 axis in acute-on-chronic liver failure(ACLF).Methods HE stai-ning and Masson's trichrome staining were used to assess hepatic inflammatory infiltration and fibrosis.Immunofluores-cence staining was performed to detect IL-6 expression in hepatic macrophages.Flow cytometry was applied to evaluate the phenotypes and functions of monocytes/macrophages and NK cells.Recombinant IL-6 was used to treat peripheral blood mononuclear cells,and PD-L1 expression on monocytes was examined.Monocytes and NK cells were co-cul-tured,and after PD-1 blockade,NK cell effector function was evaluated.Results The ACLF patients,the degree of hepatic fibrosis increased with higher serum IL-6 level.Hepatic macrophages secreted more IL-6,and the circulating monocytes showed an increased percentage[(9.89±0.65)％],absolute count[(0.58±0.04)× 106/mL],prolif-erative capacity[(36.65±6.810)％],and IL-6 secretion[(16.97±2.387)％].In ACLF mice,hepatic inflamma-tory infiltration and fibrosis were aggravated,and IL-6+macrophages exhibited enhanced pro-inflammatory activity.IL-6 had mediated the upregulation of PD-L1 expression in monocytes,while NK cells showed increased PD-1 expression and impaired effector function.When monocytes and NK cells were co-cultured,PD-1 blockade restored,NK cell ef-fector functions.Conclusion In ACLF,elevated IL-6 levels were associated with hepatic fibrosis and disease severi-ty.IL-6 mediated monocytes-induced suppression of NK cell effector functions via the PD-L1/PD-1 axis,suggesting that IL-6 plays a critical role in ACLF-related immune dysregulation.
