Chemokine Dynamics in Hepatic Disease

Chemokines are key mediators of immune cell trafficking that orchestrate both inflammatory and repair processes within the liver. In healthy tissue, low‐level chemokine expression maintains immune surveillance and vascular homeostasis. Following acute or chronic injury, hepatocytes, Kupffer cells and hepatic stellate cells rapidly up‐regulate distinct chemokine profiles, generating local gradients that recruit neutrophils, monocytes and lymphocytes. Persistent chemokine signalling drives activation of quiescent stellate cells into collagen‐secreting myofibroblasts, promoting fibrogenesis and architectural remodelling. Distinct C–C and C–X–C chemokines contribute to steatosis, steatohepatitis and cirrhosis via autocrine and paracrine loops, while their receptors (for example CCR2 and CCR5) represent targets for receptor antagonism. Therapeutic modulation of chemokine axes holds promise for reducing hepatic inflammation, limiting fibrosis progression and restoring metabolic function. Understanding the temporal and spatial dynamics of chemokine networks is therefore critical for the development of next‐generation interventions in nonalcoholic fatty liver disease, viral hepatitis and other global liver disorders.

Research from Nature Portfolio

Studies have revealed that activated hepatic stellate cells secrete CCL5 in early nonalcoholic steatohepatitis, directly inducing lipid accumulation and pro‐inflammatory gene expression in neighbouring hepatocytes via CCR5 engagement. This insight extends the established pro‐fibrotic role of CCL5 into steatosis, highlighting stellate–hepatocyte cross‐talk at pre‐fibrotic stages. Another investigation identified interferon gamma–induced protein 10 (IP-10, also known as CXCL10) as a circulating marker that correlates with insulin resistance and progressive liver injury in fatty liver disease. Elevated IP-10 levels were shown to predict incident diabetes in patients with nonalcoholic fatty liver disease, suggesting its utility as a non‐invasive biomarker for disease monitoring and risk stratification.

Chemokine Dynamics in Hepatic Disease publication trend

The graph below shows the total number of articles in chemokine dynamics in hepatic disease across all publications each year (not limited to Nature Index journals).

Technical terms

Chemokine: A small secreted protein that directs migration of immune cells along concentration gradients.

Hepatic stellate cell (HSC): A liver pericyte that transforms into a collagen‐producing myofibroblast during injury.

Kupffer cell: The resident liver macrophage responsible for clearance of pathogens and apoptotic cells.

CCR5: A G protein‐coupled chemokine receptor binding ligands such as CCL5, mediating monocyte and lymphocyte recruitment.

IP-10 (CXCL10): A C–X–C chemokine induced by interferon γ that attracts T cells and is elevated in metabolic and inflammatory liver disease.

References

1. Tropifexor plus cenicriviroc combination versus monotherapy in nonalcoholic steatohepatitis: Results from the phase 2b TANDEM study. Hepatology (2023).
2. Revealing immune infiltrate characteristics and potential immune-related genes in hepatic fibrosis: based on bioinformatics, transcriptomics and q-PCR experiments. Frontiers in Immunology (2023).
3. Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis. Scientific Reports (2018).
4. Interferon gamma-induced protein 10 is associated with insulin resistance and incident diabetes in patients with nonalcoholic fatty liver disease. Scientific Reports (2015).
5. Chemokines in Non-alcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis. Frontiers in Immunology (2020).