Montreal, October 26, 2018 – Naglaa Shoukry, Ph. D., and her team have made a significant breakthrough in their research aiming to limit the progression of liver disease. They have characterized the mechanisms of action of type 3 inflammatory cytokines that are produced by the cells of the immune system, which result in a progression of hepatic scarring known as fibrosis. These research efforts have identified new potential targets to inhibit the progression of liver disease and prevent cancer.

Researchers from the liver immunology research unit of the University of Montreal Hospital Research Center (CRCHUM) have discovered how a protein called interleukin 22 (IL-22) accelerates fibrosis during episodes of chronic hepatitis by amplifying the signal of the fibrogenic cytokine TGF-β. The fibrogenic nature of IL-22 had been unknown up to now. The new finding allows us to understand its interaction when combined with TGF-β, a cytokine that is produced during liver inflammation. Indeed, cases of advanced fibrosis confirm the pathogenic aspect of IL-22.

Another type 3 cytokine, namely interleukin 17A (IL-17A), had been known as an agent amplifying the inflammation and fibrosis leading to liver cirrhosis, which can cause cancer. The team has identified neutrophils and mast cells as the prime source of IL-17A in humans. Indeed, their number increases in inflammation induced by the immune system during liver disease.

It appears now that two type 3 cytokines, IL-17A and IL-22, can by independent mechanisms sensitize hepatic stellate cells (HSC) to the action of TGF-β. The HSCs, thus more sensitized to signals of proliferation and fibrosis, remodel the extracellular matrix leading to a deterioration of the architecture and function of the affected patient’s liver.

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