title: A deleterious role for Th9/IL-9 in hepatic fibrogenesis.
abstract: T helper 9 (Th9) cells, a recently recognized Th cell subset, are involved in autoimmune diseases. We aimed to investigate the role of Th9/interleukin-9 (IL-9) in the pathogenesis of hepatic fibrosis. Th9 and Th17 cells were quantified in chronic hepatitis B (CHB) patients with hepatic fibrosis, HBV-associated liver cirrhosis (LC) patients and healthy controls (HC). The percentages of Th9 and Th17 cells, concentrations of IL-9 and IL-17, as well as expression of IL-17, TNF-α, IL-6, IL-4, IL-21, TGF-β1 and IFN-γ were significantly increased in plasma of CHB and LC patients compared with those in HC. Splenic Th9 and Th17 cells, plasma concentrations and liver expression of IL-9 and IL-17A were significantly elevated in mice with hepatic fibrosis compared with controls. Neutralization of IL-9 in mice ameliorated hepatic fibrosis, attenuated the activation of hepatic stellate cells, reduced frequencies of Th9, Th17 and Th1 cells in spleen, and suppressed expression of IL-9, IL-17A, IFN-γ, TGF-β1, IL-6, IL-4 and TNF-α in plasma and liver respectively. Our data suggest a deleterious role of Th9/IL-9 in increasing hepatic fibrosis and exacerbating disease endpoints, indicating that Th9/IL9 based immunotherapy may be a promising approach for treating hepatic fibrosis.
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Shan-yu
authors.initials: SY
authors.lastname: Qin
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Dong-hong
authors.initials: DH
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Xiao-yun
authors.initials: XY
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Bang-li
authors.initials: BL
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Jia-xu
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Shi-Jia
authors.initials: SJ
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Xian-wen
authors.initials: XW
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Hai-xing
authors.initials: HX
authors.lastname: Jiang
authors.affiliation: Systems Immunity University Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff, UK.|Minerva Foundation Institute for Medical Research, Helsinki, Finland.
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000378:metabolism; D016906:Interleukin-9 / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D016207:Cytokines; D020381:Interleukin-17; D016906:Interleukin-9; D012333:RNA, Messenger