Functional relevance of the IL-23-IL-17 axis in lungs in vivo

Am J Respir Cell Mol Biol. 2007 Apr;36(4):442-51. doi: 10.1165/rcmb.2006-0020OC. Epub 2006 Dec 1.


It is known that interleukin (IL)-23, an IL-12-family cytokine, can be released by certain antigen-presenting cells in response to bacterial pathogens. Recent in vitro studies indicate that this cytokine stimulates a unique subset of CD4 cells, the T helper cell (Th)17 subset, to produce and release the proinflammatory cytokine IL-17. However, it has not been known whether this is an action of IL-23 per se that has bearing for the early innate response in lungs in vivo and whether there is an IL-23-responsive population of IL-17-producing CD4 cells in the bronchoalveolar space. We now present evidence that IL-23 can be involved in the early innate response to both gram-negative and gram-positive bacterial products in the lungs: Recombinant IL-23 protein per se accumulates inflammatory cells in the bronchoalveolar space in part via endogenous production of IL-17, and this IL-17 production occurs locally in IL-23-responsive CD4 cells. This IL-17 response to IL-23 occurs without any pronounced impact on Th1/Th2 polarization. Moreover, recombinant IL-23 protein increases the local MMP-9 activity, which is generated by neutrophils mainly. CD4 cells in the lungs may thus respond to IL-23 from antigen-presenting cells exposed to gram-negative and gram-positive pathogens and thereby reinforce the early innate response. These findings support that IL-23 and IL-17 form a functionally relevant "immunological axis" in the lungs in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Gelatinases
  • Immunity, Innate*
  • Immunohistochemistry
  • Interleukin-17 / metabolism*
  • Interleukin-23 / metabolism
  • Interleukin-23 / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Lung / drug effects
  • Lung / immunology*
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / physiology
  • Peptidoglycan / pharmacology


  • Interleukin-17
  • Interleukin-23
  • Lipopolysaccharides
  • Peptidoglycan
  • Gelatinases