Interleukin-17 contributes to the pathogenesis of autoimmune hepatitis through inducing hepatic interleukin-6 expression

• Published in: PloS one 2011-04, Vol.6 (4), p.e18909-e18909
• Main Authors: Zhao, Li, Tang, Yanli, You, Zhengrui, Wang, Qixia, Liang, Shuwen, Han, Xiaofeng, Qiu, Dekai, Wei, Jue, Liu, Yuan, Shen, Lei, Chen, Xiaoyu, Peng, Yanshen, Li, Zhiping, Ma, Xiong
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adolescent; Adult; Arthritis; Autoimmune diseases; Autoimmunity; Biology; Biopsy; Case-Control Studies; Chemokines; Chronic active hepatitis; Comparative analysis; Control theory; Cytokines; Development and progression; Effector cells; Feedback; Feedback loops; Female; Fibrosis; Gastroenterology; Gene expression; Helper cells; Hep G2 Cells; Hepatitis; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - pathology; Hepatitis, Autoimmune - blood; Hepatitis, Autoimmune - etiology; Hepatitis, Autoimmune - immunology; Hepatocytes; Hepatology; Humans; Immunity; Inflammatory bowel disease; Innate immunity; Interleukin 17; Interleukin 23; Interleukin 6; Interleukin-17 - blood; Interleukin-17 - metabolism; Interleukin-17 - pharmacology; Interleukin-23 - blood; Interleukin-6 - metabolism; Interleukin-6 - secretion; Interleukins; Liver; Liver - enzymology; Liver - immunology; Liver - metabolism; Liver - pathology; Liver diseases; Lupus; Lymphocytes; Lymphocytes T; Male; MAP kinase; MAP Kinase Signaling System - drug effects; Medical research; Medicine; Middle Aged; Mitogen-Activated Protein Kinases - metabolism; Pathogenesis; Patients; Positive feedback; Proteins; Rodents; Serum levels; Signal transduction; Signaling; T cells; Th17 Cells - drug effects; Th17 Cells - metabolism; Transcription factors; Transplants & implants; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0018909

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.