IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice

Am J Respir Crit Care Med. 2008 Nov 15;178(10):1023-32. doi: 10.1164/rccm.200801-086OC. Epub 2008 Sep 11.


Rationale: The IL-23-IL-17A-producing CD4(+) T-cell (Th17 cell) axis plays an important role in the development of chronic inflammatory diseases, including autoimmune diseases. However, the role of the IL-23-Th17 cell axis in the regulation of allergic airway inflammation is still largely unknown.

Objectives: To determine the role of IL-23 and Th17 cells in allergic airway inflammation.

Methods: We examined the effect of anti-IL-23 antibody on antigen-induced airway inflammation. We also investigated the effect of enforced expression of IL-23 on allergic airway inflammation by generating lung-specific IL-23 transgenic mice. Moreover, we examined the effect of adoptive transfer of antigen-specific Th17 cells on allergic airway inflammation.

Measurements and main results: IL-23 mRNA was expressed in the lung of sensitized mice upon antigen inhalation, and the neutralization of IL-23 decreased antigen-induced eosinophil recruitment and Th2 cytokine production in the airways. The enforced expression of IL-23 in the airways significantly enhanced antigen-induced eosinophil and neutrophil recruitment into the airways; Th2 cytokine, IL-17A, and tumor necrosis factor (TNF)-alpha production in the airways; goblet cell hyperplasia; and airway hyperresponsiveness. Moreover, IL-23-mediated enhancement of antigen-induced Th2 cytokine production and eosinophil recruitment in the airways was still observed in the mice lacking IL-17A. Furthermore, although adoptive transfer of antigen-specific Th17 cells alone induced neutrophil but not eosinophil recruitment into the airways upon antigen inhalation, cotransfer of Th17 cells with Th2 cells significantly enhanced antigen-induced Th2-cell-mediated eosinophil recruitment into the airways and airway hyperresponsiveness.

Conclusions: IL-23 and Th17 cells not only induce Th17-cell-mediated neutrophilic airway inflammation but also up-regulate Th2-cell-mediated eosinophilic airway inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / chemically induced
  • Asthma / immunology*
  • Disease Models, Animal
  • Eosinophils / immunology
  • Interleukin-17 / immunology*
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Pneumonia / immunology*
  • T-Lymphocyte Subsets / immunology*
  • Th2 Cells / immunology*
  • Up-Regulation


  • Interleukin-17
  • Interleukin-23