Spleen-Liver Interactions in Hepatic Pathophysiology

The spleen and liver engage in dynamic bidirectional communication that shapes the course of liver disease and regeneration. Via the portal circulation, splenic immune cells, cytokines and soluble mediators reach the liver, modulating inflammation, fibrogenesis and tissue repair. In chronic injury, splenic monocytes and macrophages migrate to the liver, where they interact with hepatic stellate cells and resident Kupffer cells to amplify profibrotic signalling. Splenomegaly and hypersplenism further alter systemic immune status, exacerbating portal hypertension and the progression from fibrosis to cirrhosis. Conversely, loss of splenic function through splenectomy or functional hyposplenism can recalibrate hepatic immune responses, reducing proinflammatory cytokine levels and attenuating scar formation. In acute liver resection models, spleen-derived protease inhibitors and monocytes support hepatocyte proliferation and remodelling, whereas removal of the spleen shifts the balance towards increased growth-inhibitory factors, impacting regenerative kinetics. Collectively, these findings underscore the spleen as both a source of fibrogenic drivers and a regulator of reparative processes, with implications for targeted therapies to modulate the spleen-liver axis in chronic liver disease and post-resection recovery.

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Spleen-Liver Interactions in Hepatic Pathophysiology publication trend

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Technical terms

Monocytes: Circulating white blood cells that differentiate into macrophages or dendritic cells upon entering tissues.

Macrophages: Tissue-resident or infiltrating immune cells that phagocytose debris and secrete cytokines to regulate inflammation.

Fibrogenesis: The formation of scar tissue in the liver driven by activated hepatic stellate cells and extracellular matrix deposition.

Hypersplenism: An enlarged and overactive spleen that sequesters blood cells and alters systemic immune responses.

TGF-β1: Transforming growth factor beta 1, a cytokine that promotes fibrotic activation of hepatic stellate cells.

LIGHT (TNFSF14): A tumour necrosis factor superfamily ligand involved in immune regulation and promotion of tissue fibrosis.

References

1. Intravital imaging of splenic classical monocytes modifying the hepatic CX3CR1+ cells motility to exacerbate liver fibrosis via spleen-liver axis. Theranostics (2024).
2. The spleen as a possible source of serine protease inhibitors and migrating monocytes required for liver regeneration after 70% resection in mice. Frontiers in Cell and Developmental Biology (2023).
3. The spleen in liver cirrhosis: revisiting an old enemy with novel targets. Journal of Translational Medicine (2017).
4. Spleen: Reparative Regeneration and Influence on Liver. Life (2022).
5. Splenectomy improves liver fibrosis via tumor necrosis factor superfamily 14 (LIGHT) through the JNK/TGF-β1 signaling pathway. Experimental & Molecular Medicine (2021).