Published ahead of print on September 11, 2008, doi:10.1164/rccm.200801-086OC Am. J. Respir. Crit. Care Med., Volume 178, Number 10, November 2008, 1023-1032 A more recent version of this article appeared on November 15, 2008
Submitted on January 14, 2008 IL-23 and Th17 Cells Enhance Th2 Cell-mediated Eosinophilic Airway Inflammation in MiceHidefumi Wakashin1,1 Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan; Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, Japan, 2 Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan, 3 Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan; Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan, 4 Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, Japan, 5 Department of Developmental Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan, 6 Center for Experimental Medicine, Institue of Medical Science, University of Tokyo, Tokyo, Japan, 7 Department of Experimental Medicine, University of Perugia, Perugia, Italy, 8 Research Center for Allergy and Clinical Immunology, Asahi General Hospital, Chiba, Japan * To whom correspondence should be addressed. E-mail: nakajimh{at}faculty.chiba-u.jp.
Rationale: IL-23-IL-17A producing CD4+ T cell (Th17 cell) axis plays important roles in the development of chronic inflammatory diseases including autoimmune diseases. However, the role of 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.
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 TNF- 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, co-transfer 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 upregulate Th2 cell-mediated eosinophilic airway inflammation.
