title: Interleukin-17 contributes to the pathogenesis of autoimmune hepatitis through inducing hepatic interleukin-6 expression.
abstract: T helper cells that produce IL-17 (Th17 cells) have recently been identified as the third distinct subset of effector T cells. Emerging data suggests that Th17 cells play an important role in the pathogenesis of many liver diseases by regulating innate immunity, adaptive immunity, and autoimmunity. In this study, we examine the role and mechanism of Th17 cells in the pathogenesis of autoimmune hepatitis (AIH). The serum levels of IL-17 and IL-23, as well as the frequency of IL-17+ cells in the liver, were significantly elevated in patients with AIH, compared to other chronic hepatitis and healthy controls. The hepatic expressions of IL-17, IL-23, ROR-γt, IL-6 and IL-1β in patients with AIH were also significantly increased and were associated with increased inflammation and fibrosis. IL-17 induces IL-6 expression via the MAPK signaling pathway in hepatocytes, which, in turn, may further stimulate Th17 cells and forms a positive feedback loop. In conclusion, Th17 cells are key effector T cells that regulate the pathogenesis of AIH, via induction of MAPK dependent hepatic IL-6 expression. Blocking the signaling pathway and interrupting the positive feedback loop are potential therapeutic targets for autoimmune hepatitis.
authors.affiliation: Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Yanli
authors.initials: Y
authors.lastname: Tang
authors.forename: Zhengrui
authors.initials: Z
authors.lastname: You
authors.forename: Qixia
authors.initials: Q
authors.lastname: Wang
authors.forename: Shuwen
authors.initials: S
authors.lastname: Liang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Han
authors.forename: Dekai
authors.initials: D
authors.lastname: Qiu
authors.forename: Jue
authors.initials: J
authors.lastname: Wei
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
authors.forename: Yanshen
authors.initials: Y
authors.lastname: Peng
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.forename: Xiong
authors.initials: X
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D056945:Hep G2 Cells; D019694:Hepatitis B, Chronic / Q000097:blood / Q000473:pathology; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000209:etiology* / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D053759:Interleukin-23 / Q000097:blood; D015850:Interleukin-6 / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D020928:Mitogen-Activated Protein Kinases