Targeting interleukin (IL)-17A and IL-22 proteins may help delay the development of hepatic fibrosis.
New research has identified potential targets to inhibit the progression of liver disease and prevent cancer, according to a study published in Science Immunology.
From 2000 to 2015, death rates for chronic liver disease and cirrhosis in the United States increased 31%, according to the CDC. Chronic liver disease and cirrhosis can contribute to the development of liver cancer, which affects approximately 33,000 individuals in the United States each year.
For the study, scientists from the liver immunology research unit of the University of Montreal Hospital Research Center evaluated the contribution of the type 3 cytokines interleukin (IL)-17A and IL-22 to the progression of liver fibrosis. Type 3 inflammation, which is characterized by the production of IL-17A and IL-22, is implicated in many inflammatory conditions of the gut and can be counteracted by regulatory T cells, but its contribution to liver fibrosis is poorly understood, according to the study.
By profiling the cytokines produced by intrahepatic lymphocytes (IHLs) from liver biopsies of patients with viral hepatitis and nonviral hepatitis, the researchers found that both type 3 cytokines can sensitize hepatic stellate cells (HSC) to the action of transforming growth factor (TGF)-β, a cytokine that is produced during liver inflammation.
According to the researchers, the study showed that the IL-22 protein appeared to accelerate fibrosis during episodes of chronic hepatitis by amplifying the fibrogenic cytokine TGF-β. Until now, the fibrogenic nature of IL-22 has been unknown. Additionally, the researchers found that production of IL-17A, which is known to amplify inflammation and fibrosis leading to liver cirrhosis, was driven by neutrophils and mast cells in humans.
“Our data suggest that dysregulation of type 3 inflammation during chronic liver injury is one of the key mechanisms of fibrogenesis in humans, and we identified neutrophils and mast cells as major producers of IL-17 in this setting,” the researchers wrote in the study.
Experimental mouse models have indicated that the inhibition of IL-17A and IL-22 can delay the development of hepatic fibrosis, which may lead to potential new therapies that could intervene in fibrosis development and prevent liver cancer, according to the researchers. They concluded that the findings determine that targeting IL-17 and IL-22 can limit liver fibrosis, but noted that additional research with prolonged treatment and different treatment regimens applied during various stages of liver injury is needed.
Fabre T, Flores M, Soucy G, et al. Type 3 cytokines IL-17A and IL-22 drive TGF-β-dependent liver fibrosis. Science Immunology. 2018. Doi: 10.1126/sciimmunol.aar7754.