Published ahead of print on September 11, 2008, doi:10.1164/rccm.200801-086OC
© 2008 American Thoracic Society doi: 10.1164/rccm.200801-086OC
IL-23 and Th17 Cells Enhance Th2-Cell–mediated Eosinophilic Airway Inflammation in Mice1 Department of Allergy and Clinical Immunology, Chiba University Hospital, and 2 Department of Clinical Cell Biology, 3 Department of Molecular Genetics, 4 Department of Developmental Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan; 5 Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan; 6 Department of Experimental Medicine, University of Perugia, Perugia, Italy; and 7 Research Center for Allergy and Clinical Immunology, Asahi General Hospital, Chiba, Japan Correspondence and requests for reprints should be addressed to Hiroshi Nakajima, M.D., Ph.D., Department of Molecular Genetics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba 260-8670, Japan. E-mail: nakajimh{at}faculty.chiba-u.jp 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)- 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.
Key Words: allergy • cytokines • eosinophils • transgenic/knockout mice
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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. 
