IL-22 is essential for lung epithelial repair following influenza infection

Am J Pathol. 2013 Apr;182(4):1286-96. doi: 10.1016/j.ajpath.2012.12.007. Epub 2013 Mar 11.


Influenza infection is widespread in the United States and the world. Despite low mortality rates due to infection, morbidity is common and little is known about the molecular events involved in recovery. Influenza infection results in persistent distal lung remodeling, and the mechanism(s) involved are poorly understood. Recently IL-22 has been found to mediate epithelial repair. We propose that IL-22 is critical for recovery of normal lung function and architecture after influenza infection. Wild-type and IL-22(-/-) mice were infected with influenza A PR8/34 H1N1 and were followed up for up to 21 days post infection. IL-22 receptor was localized to the airway epithelium in naive mice but was expressed at the sites of parenchymal lung remodeling induced by influenza infection. IL-22(-/-) mice displayed exacerbated lung injury compared with wild-type mice, which correlated with decreased lung function 21 days post infection. Epithelial metaplasia was observed in wild-type mice but was not evident in IL-22(-/-) animals that were characterized with an increased fibrotic phenotype. Gene expression analysis revealed aberrant expression of epithelial genes involved in repair processes, among changes in several other biological processes. These data indicate that IL-22 is required for normal lung repair after influenza infection. IL-22 represents a novel pathway involved in interstitial lung disease.

Publication types

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

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Basement Membrane / pathology
  • Collagen / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Epithelium / metabolism
  • Epithelium / pathology*
  • Epithelium / virology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Interleukins / deficiency
  • Interleukins / metabolism*
  • Lung / pathology*
  • Lung / physiopathology
  • Lung / virology*
  • Metaplasia
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / pathology*
  • Orthomyxoviridae Infections / physiopathology
  • Orthomyxoviridae Infections / virology
  • Receptors, Interleukin / metabolism
  • Respiratory Function Tests
  • Signal Transduction / genetics
  • Wound Healing*


  • Interleukins
  • Receptors, Interleukin
  • interleukin-22 receptor
  • Collagen
  • interleukin-22