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Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression

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....

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079758/
https://www.ncbi.nlm.nih.gov/pubmed/21526159
http://dx.doi.org/10.1371/journal.pone.0018909
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author 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
author_facet 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
author_sort Zhao, Li
collection PubMed
description 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.
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spelling pubmed-30797582011-04-27 Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression 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 PLoS One Research Article 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. Public Library of Science 2011-04-19 /pmc/articles/PMC3079758/ /pubmed/21526159 http://dx.doi.org/10.1371/journal.pone.0018909 Text en Zhao et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression
title Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression
title_full Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression
title_fullStr Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression
title_full_unstemmed Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression
title_short Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression
title_sort interleukin-17 contributes to the pathogenesis of autoimmune hepatitis through inducing hepatic interleukin-6 expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079758/
https://www.ncbi.nlm.nih.gov/pubmed/21526159
http://dx.doi.org/10.1371/journal.pone.0018909
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