Human hepatic stellate cells, hepatocytes, and immune cells – indirect modulation via paracrine factors

This target entry describes the complex intercellular communication network within the liver microenvironment, involving hepatic stellate cells (HSCs), hepatocytes, and immune cells such as Kupffer cells (Tsuchida & Friedman, 2017, Cell Mol Gastroenterol Hepatol). In the context of chronic liver injury, hepatocytes release paracrine signals and damage-associated molecular patterns (DAMPs) that recruit and activate immune cells (Kisseleva & Brenner, 2021, Nat Rev Gastroenterol Hepatol). These immune cells then secrete pro-fibrogenic cytokines, most notably TGF-beta, which trigger the activation of HSCs into collagen-producing myofibroblasts (Bataller & Brenner, 2005, J Clin Invest). Rather than a single molecule, this represents a systems-level therapeutic approach where drugs aim to interrupt the indirect activation of HSCs by modulating the secretome of neighboring cells (Pellicoro et al., 2014, Nat Rev Immunol). This paracrine modulation is a central focus in the development of treatments for nonalcoholic steatohepatitis (NASH) and advanced liver fibrosis.

Other names

Liver microenvironment crosstalkHSC-hepatocyte-immune cell axisParacrine signaling in liver fibrosisHepatic cellular niche modulationIntrahepatic paracrine signaling

Indirect modulation of hepatic stellate cell activation through the regulation of paracrine signaling molecules (cytokines, chemokines, and growth factors) secreted by hepatocytes and immune cells.