Journal Article

IL-23 and Th17 Cells Enhance Th2-Cell-mediated Eosinophilic Airway Inflammation in Mice

Nakajima, Hiroshi, Wakashin, Hidefumi, Iwamoto, Itsuo, Hirose, Koichi, Watanabe, Norihiko, Tokuhisa, Takeshi, Saito, Yasushi, Puccetti, Paolo, Kagami, Shin-ichiro, Suto, Akira, Hatano, Masahiko, Iwakura, Yoichiro, Maezawa, Yuko

2008

Overview

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. To determine the role of IL-23 and Th17 cells in allergic airway inflammation. 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. 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. IL-23 and Th17 cells not only induce Th17-cell-mediated neutrophilic airway inflammation but also up-regulate Th2-cell-mediated eosinophilic airway inflammation.

• Publisher: Am Thoracic Soc,American Lung Association,Oxford University Press
• Subject: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Animals / Antigens / Asthma / Asthma - chemically induced / Asthma - immunology / Biological and medical sciences / Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis / Cytokines / Disease Models, Animal / Eosinophils - immunology / Inflammation / Intensive care medicine / Interleukin-17 - immunology / Interleukin-23 - immunology / Interleukin-23 - metabolism / Lymphocytes / Medical sciences / Mice / Mice, Knockout / Mice, Transgenic / Neutrophils / Pneumonia - immunology / Polymerase chain reaction / T-Lymphocyte Subsets - immunology / Th2 Cells - immunology / Transfusions. Complications. Transfusion reactions. Cell and gene therapy / Transgenic animals / Tumor necrosis factor-TNF / Up-Regulation