BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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 HBVtransgenic mice and measured levels of IL-22 in HBV-infectedpatients. RESULTS: In HBVtransgenic 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 HBVtransgenic 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: M H Xie; S Aggarwal; W H Ho; J Foster; Z Zhang; J Stinson; W I Wood; A D Goddard; A L Gurney Journal: J Biol Chem Date: 2000-10-06 Impact factor: 5.157
Authors: Luca G Guidotti; Amber Morris; Heike Mendez; Rick Koch; Robert H Silverman; Bryan R G Williams; Francis V Chisari Journal: J Virol Date: 2002-03 Impact factor: 5.103
Authors: Giovanni Sitia; Masanori Isogawa; Matteo Iannacone; Iain L Campbell; Francis V Chisari; Luca G Guidotti Journal: J Clin Invest Date: 2004-04 Impact factor: 14.808
Authors: Giovanni Sitia; Masanori Isogawa; Kazuhiro Kakimi; Stefan F Wieland; Francis V Chisari; Luca G Guidotti Journal: Proc Natl Acad Sci U S A Date: 2002-10-04 Impact factor: 11.205