Research ArticleFIBROSIS

Type 3 cytokines IL-17A and IL-22 drive TGF-β–dependent liver fibrosis

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Science Immunology  26 Oct 2018:
Vol. 3, Issue 28, eaar7754
DOI: 10.1126/sciimmunol.aar7754

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Type 3 injury

Chronic liver injury caused by infection, toxins, or other inflammatory conditions can lead to liver fibrosis. Several cytokines have been linked to liver fibrosis, and here, Fabre et al. define a role for the type 3 cytokines interleukin-17A (IL-17A) and IL-22 in driving transforming growth factor–β (TGF-β)–dependent fibrosis. They observed elevated levels of IL-17A and IL-22 in intrahepatic lymphocytes from patients with hepatitis. Hepatic stellate cells treated with IL-22 showed enhanced p38 mitogen-activated protein kinase–dependent TGF-β signaling. Liver-resident neutrophils and mast cells were identified as the primary sources of IL-17 in humans, and mouse studies showed that blockade of IL-17A and IL-22 could reduce fibrosis. Together, these findings define a role for type 3 cytokines in driving fibrosis during liver injury.