# Hepatitis C virus core protein-induced myeloid-derived suppressor cells promote hepatic fibrosis by regulating hepatic stellate cell function via TGF-β

## TL;DR

This study shows how the hepatitis C virus promotes liver fibrosis by influencing immune cells and liver cells through a specific signaling pathway.

## Contribution

The study identifies a new mechanism linking HCV infection, MDSCs, and liver fibrosis via TGF-β signaling.

## Key findings

- HCV core protein induces monocytes to become MDSCs.
- MDSCs promote liver cell proliferation and collagen production while blocking apoptosis.
- Blocking TGF-β signaling reduces these effects, suggesting a therapeutic target.

## Abstract

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.