title: Involvement of the Interleukin-23/Interleukin-17 Axis in Chronic Hepatitis C Virus Infection and Its Treatment Responses.
abstract: Interleukin-23 (IL-23) and its downstream factor IL-17 are the key cytokines involved in immune and inflammatory response in chronic liver diseases. This study aimed to investigate the role and molecular mechanisms of the IL-23/Th17 axis in chronic hepatitis C virus (HCV) infection, and the efficacy of IL-23/Th17 modulation in response to anti-HCV therapy. Sixty-six HCV-infected patients and 20 healthy controls were enrolled. The patients received PegIFNa-2a and ribavirin therapy for at least 48 weeks. The plasma level of IL-23 and the number of IL-17A-, IFN-γ-, and IL-21-producing peripheral blood mononuclear cells (PBMCs) at baseline and 12, 24, and 48 weeks following treatment were determined. The mRNA level of Th17 immune-associated molecules in PBMCs was evaluated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) following treatment with IL-23 agonist or antagonist. Our data showed that, compared to healthy controls, HCV-infected patients had an increased plasma level of IL-23 and increased frequencies of IL-17A- and IFN-γ-producing PBMCs, whereas the HCV patients exhibited a reduced number of IL-21-producing PBMCs. However, the baseline frequencies of IL-21-producing PBMCs were markedly higher in HCV patients who achieved rapid virological response (RVR) than those without RVR. Additionally, the mRNA expressions of IL-21, IFN-γ, myxovirus resistance protein A (MxA), and suppressor of cytokine signaling 3 (SOCS3) were significantly upregulated in PBMCs, while FoxP3 expression was suppressed by IL-23 agonist. Thus, the IL-23/Th17 axis plays an important role in development of chronic HCV infection and antiviral response. IL-23 may enhance the antiviral activity of interferon-based therapy by modulating the expression of Th17 cells-associated molecules in HCV-infected patients.
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050000, China. mengping8547@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Meng
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050000, China. sxzhao76@163.com.
authors.forename: Suxian
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050000, China. niuxuemin322@163.com.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Niu
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050000, China. funa418@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Fu
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050000, China. sushanshan1002@126.com.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Su
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050000, China. wangrongqiw@163.com.
authors.forename: Rongqi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050000, China. zygyxa@126.com.
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research (WIMR), the University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia. liang.qiao@sydney.edu.au.
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050000, China. nanyuemin@163.com.
authors.forename: Yuemin
authors.initials: Y
authors.lastname: Nan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D012254:Ribavirin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D020381:Interleukin-17; D053759:Interleukin-23; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
keywords: T helper 17 cells; hepatitis C virus; interferon-γ; interleukin-23; myxovirus resistance protein A