Roles of hepatic stellate cells in liver inflammation: a new perspective

Connected with the intestinal tract through the portal circulation, liver sinusoids function as the first line of defense against extrahepatic stimuli such as bacterial products and other toxic substances. Hepatic stellate cells (HSCs) are pericytes residing in the perisinusoidal space, between sinusoidal endothelial cells and hepatocytes, store vitamin A, and regulate sinusoidal circulation. Following chronic hepatitis, HSCs actively produce extracellular matrices and cause liver fibrosis. In spite of their close position to the liver sinusoids, however, whether HSCs contribute to liver inflammation has remained elusive. Evidence now accumulates to suggest that HSCs actively take part in the regulation of various forms of liver inflammation. Upon inflammatory stimuli from the sinusoids, HSCs produce various inflammatory molecules and interact with other liver cells, thereby recruiting and then activating infiltrating leukocytes and ultimately causing hepatocyte death. On the other hand, HSCs also exert hepatoprotective effects through inhibition of cytokine and chemokine production or induction of immunosuppressive cell population. HSCs therefore integrate cytokine-mediated inflammatory responses in the sinusoids and relay them to the liver parenchyma, either amplifying liver inflammation or suppressing parenchymal damage through immunoregulatory signaling depending on the context.