A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus

Gastroenterology. 2011 Nov;141(5):1897-906. doi: 10.1053/j.gastro.2011.06.051. Epub 2011 Jun 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Animals
  • Case-Control Studies
  • Disease Models, Animal
  • Female
  • Hepatitis B / immunology*
  • Hepatitis B / metabolism
  • Hepatitis B / physiopathology
  • Hepatitis B virus / immunology*
  • Hepatitis B virus / physiology
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / metabolism
  • Hepatitis B, Chronic / physiopathology
  • Humans
  • Immunity, Innate / physiology*
  • Interferon-gamma / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Severity of Illness Index
  • Th17 Cells / pathology
  • Virus Replication / physiology


  • Interleukins
  • Interferon-gamma
  • interleukin-22