title: Pathological functions of interleukin-22 in chronic liver inflammation and fibrosis with hepatitis B virus infection by promoting T helper 17 cell recruitment.
abstract: It is well established that interleukin (IL)-22 has hepatoprotective and antifibrotic functions in acute liver injury models; however, its function in patients with liver fibrosis and liver cirrhosis (LC) remains obscure. In the current study, we demonstrated that expression of numerous IL-22 pathway-associated genes was significantly up-regulated in hepatitis B virus (HBV)-infected liver tissues, compared to normal controls, through microarray analysis. In agreement with these findings, liver-infiltrating IL-22(+) cells were largely increased in HBV-infected patients with LC, compared to those without LC or healthy subjects, and were positively associated with liver fibrosis staging scores. Immunohistochemistry and flow cytometric analyses revealed that IL-22 was produced by multiple intrahepatic immune cells and, preferentially, by T-helper (Th) 17 cells in LC patients. In an HBV transgenic (Tg) mouse model of T-cell-mediated chronic liver inflammation and fibrosis, blockade of IL-22 attenuated hepatic expression of chemokine (C-X-C motif) ligand 10 and chemokine (C-C motif) ligand 20 (CCL20) and subsequently reduced Th17 recruitment and liver inflammation and fibrosis progression. In vitro treatment with IL-22 stimulated hepatic stellate cells (HSCs) to secrete several chemokines and subsequently promoted Th17 cell chemotaxis. Blocking C-X-C chemokine receptor type 3 or CCL20 reduced Th17 cell chemotaxis by IL-22-treated HSCs.
  
  
  CONCLUSIONS
  IL-22 plays a pathological role in exacerbating chronic liver inflammation and fibrosis by recruiting hepatic Th17 cells in HBV-infected patients and HBV Tg mice.
authors.affiliation: Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Zhao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Luan
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Zou
authors.forename: Yanling
authors.initials: Y
authors.lastname: Sun
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Chunbao
authors.initials: C
authors.lastname: Zhou
authors.forename: Junliang
authors.initials: J
authors.lastname: Fu
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.forename: Yangxin
authors.initials: Y
authors.lastname: Fu
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002452:Cell Count; D054418:Chemokine CCL20 / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D002908:Chronic Disease; D015897:Comorbidity; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000473:pathology; D006509:Hepatitis B / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology*; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology*; D058504:Th17 Cells / Q000473:pathology*; D000097043:Interleukin-22
chemical_list: D054418:Chemokine CCL20; D007378:Interleukins; D000097043:Interleukin-22