Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells

Interleukin-33 in the pathogenesis of liver fibrosis: alarming ILC2 and hepatic stellate cells

“…5 First, the authors confirmed that IL-33 is increased in bile duct ligation (BDL)-induced fibrosis in mice and in human cirrhotic liver tissue, which is in line with the current body of literature. 1,2, 6 Parenchymal cells (that is, hepatocytes) were the primary cellular source of IL-33.…”

“…However, IL-33 alone failed to enhance the inflammatory response in sham-operated mice, suggesting that IL-33 has the capacity to increase the production of inflammatory cytokines only in injured livers. 5 In accordance with this role, recombinant IL-33 aggravated hepatic fibrosis in experimental steatohepatitis, but had beneficial effects on hepatic steatosis. 7 In addition, Tan et al provide experimental evidence that IL-33/ST2 signaling is critical in activated hepatic stellate cells, the primary matrix-producing cells in the liver.…”

“…This resulted in the stimulation of α-smooth muscle actin and collagen expression. 5 These data suggest a direct profibrogenic role of IL-33 in hepatic stellate cells, which is potentially synergistic with its effects on innate lymphoid cells type 2 (ILC2). 1 Although the current study and complementary fibrosis studies demonstrate overall profibrogenic effects in chronic injury models, studies in acute injury settings sharply contradict this notion.…”

“…and markers of hepatic fibrogenesis (that is, α-smooth muscle actin (α-SMA), collagen) in activated and transdifferentiated HSC (referred to as myofibroblasts (MFB)). 5 …”

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“…AREG induced proliferation, survival and ECM production of HSCs [39] thereby stimulating their pro-fibrogenic activity that may result in development of cirrhosis with progression to HCC. Unlike Kupffer cells that do not express ST2 [40], HSCs express the IL-33 receptor and become activated by IL-33 as shown in murine bile-duct ligation-induced hepatic fibrosis [41], pointing to another mechanism by which IL-33 drives chronic inflammation and tissue remodeling in the liver.…”