# CX3CL1/CX3CR1 axis in liver disease: context-dependent roles and balance

## TL;DR

This review explores how the CX3CL1/CX3CR1 axis plays different roles in liver diseases, depending on the context, and discusses its potential for precision medicine.

## Contribution

The paper introduces a contextual signaling model to explain the dual roles of the CX3CL1/CX3CR1 axis in liver diseases.

## Key findings

- The CX3CL1/CX3CR1 axis shows both pro- and anti-inflammatory effects in liver diseases.
- Its role varies across different liver conditions like NAFLD, hepatitis, and liver cancer.
- The axis has potential as a biomarker but faces challenges in translation to therapy.

## Abstract

This review provides a systematic and critical examination of the multifaceted roles of the CX3CL1/CX3CR1 axis in liver diseases. We emphasize its context-dependent duality—exhibiting both pro- and anti-inflammatory, pro- and anti-fibrotic, and pro- and anti-tumor functions across different etiologies. Moving beyond a binary good or bad” paradigm, we propose a contextual signaling model that integrates cellular source, microenvironmental cues, and intersecting pathways to explain its divergent roles. We synthesize recent advances in its involvement in NAFLD/NASH, viral hepatitis, autoimmune hepatitis, schistosomiasis, liver fibrosis and hepatocellular carcinoma. The review critically evaluates the axis’s potential as a biomarker, discusses methodological advances and limitations in human studies, and analyzes therapeutic strategies with a focus on translational challenges. We conclude with a forward-looking perspective on precision medicine approaches targeting this axis.