Hepatitis C virus core protein-induced myeloid-derived suppressor cells promote hepatic fibrosis by regulating...

Myeloid-derived suppressor cells (MDSCs) constitute a population of cells with immunosuppressive functions, potentially playing a pivotal role in the progression of chronic hepatitis C (CHC) to liver fibrosis. This study aimed to elucidate the molecular mechanisms by which HCVc-induced MDSCs interact with hepatic stellate cells to influence the onset and progression of liver fibrosis.

CD14⁺ monocytes were isolated and purified from healthy human peripheral blood. These cells were stimulated in vitro with hepatitis C virus core protein (HCVc) to induce differentiation into MDSCs. CD14⁺ monocytes or HCVc-induced MDSCs were co-cultured with the human hepatic stellate cell line LX2 to establish an in vitro co-culture system. The TGF-β signaling pathway was blocked using a neutralizing antibody. LX2 proliferation was assessed via the MTT assay, LX2 activation via ELISA, and LX2 apoptosis via flow cytometry.

HCVc induced CD14⁺ monocytes to differentiate into MDSCs. HCVc-induced MDSCs promoted LX2 proliferation and type I collagen (Col-1) synthesis while inhibiting LX2 apoptosis, thereby driving the onset and progression of liver fibrosis. This effect was suppressed by TGF-β neutralizing antibodies.

HCVc-induced MDSCs mediate the regulation of LX2 proliferation, activation, and apoptosis via TGF-β signaling, thereby promoting hepatic fibrosis. This "HCVc-MDSCs-TGF-β-LX2" axis establishes, for the first time, a direct link between viral infection, immunosuppressive myeloid cells, and the hepatic fibrosis process, providing potential targets for developing novel therapeutic strategies for hepatitis C-associated liver fibrosis.