title: A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus.
abstract: OBJECTIVE
  T-helper (Th)17 cells that secrete interleukin (IL)-22 have immunomodulatory and protective properties in the liver and other tissues. IL-22 induces expression of proinflammatory genes but is also mitogenic and antiapoptotic in hepatocytes. Therefore, it could have multiple functions in the immune response to hepatitis B virus (HBV).
  
  
  METHODS
  We examined the role of IL-22 in regulating liver inflammation in HBV transgenic mice and measured levels of IL-22 in HBV-infected patients.
  
  
  RESULTS
  In HBV transgenic mice, injection of a single dose of IL-22 increased hepatic expression of proinflammatory genes but did not directly inhibit virus replication. When splenocytes from HBV-immunized mice were transferred into HBV transgenic mice, the severity of the subsequent liver damage was ameliorated by neutralization of IL-22. In this model, IL-22 depletion did not affect interferon gamma-mediated noncytopathic inhibition of virus replication initiated by HBV-specific cytotoxic T cells, but it significantly inhibited recruitment of antigen-nonspecific inflammatory cells into the liver. In patients with acute HBV infections, the percentage of Th17 cells in peripheral blood and concentration of IL-22 in serum were significantly increased.
  
  
  CONCLUSIONS
  IL-22 appears to be an important mediator of the inflammatory response following recognition of HBV by T cells in the liver. These findings might be relevant to the development of cytokine-based therapies for patients with HBV infection.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520-8023, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Cobleigh
authors.forename: Jian-Qi
authors.initials: JQ
authors.lastname: Lian
authors.forename: Chang-Xing
authors.initials: CX
authors.lastname: Huang
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Booth
authors.forename: Xue-Fan
authors.initials: XF
authors.lastname: Bai
authors.forename: Michael D
authors.initials: MD
authors.lastname: Robek
mesh_terms: D000208:Acute Disease; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D006509:Hepatitis B / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006515:Hepatitis B virus / Q000276:immunology* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012720:Severity of Illness Index; D058504:Th17 Cells / Q000473:pathology; D014779:Virus Replication / Q000502:physiology; D000097043:Interleukin-22
chemical_list: D007371:Interferon-gamma; D007378:Interleukins; D000097043:Interleukin-22