| Project/Area Number |
18604003
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
アレルギー
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| Research Institution | Chiba University |
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Principal Investigator |
HIROSE Koichi Chiba University, University Hospital, Dept of Allergy and clinical Immunology, Assistant Professor (90400887)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Hiroshi Chiba University, Graduate School of Meclicine, Dept of Molecular Genetics, Professor (00322024)
WATANABE Norihiko Chiba University, University Hospital, Dept of Allergy and clinical Immunology, Associate Prof (20375653)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,080,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | asthma / eosinophilic inflammation / IL-23 / IL-17 / Th17 / neutrophilic inflammation |
|---|
| Research Abstract |
IL-23-IL-17 producing CD4^+ T cell (Th17 cell) axis seems to play an important role in the development of chronic inflammatory diseases including autoimmune diseases. In this study, we show that IL-23 and Th17 cells enhance Th2 cell-mediated allergic airway inflammation using a mouse model of asthma. We found that IL-23 mRNA was expressed in the lung of sensitized mice upon antigen inhalation. We also found that neutralization of IL-23 decreased antigen-induced eosinophil recruitment and Th2 cytokine production in the airways. Furthermore, the enforced expression of IL-23 in the airways significantly enhanced antigen-induced eosinophil recruitment and Th2 cytokine production in the airways, goblet cell hyperplasia, and airway hyperresponsiveness. Moreover, although adoptive transfer of antigen-specific Th17 cells alone did not induce eosinophil recruitment into the airways upon antigen inhalation, the cotransfer of Th17 cells with Th2 cells significantly enhanced antigen-induced, Th2 cell-mediated eosinophil recruitment into the airways. These results suggest that IL-23-Th17 cell axis upregulates Th2 cell-mediated eosinophilic airway inflammation by at least two mechanisms; IL-23 enhances the activation of Th2 cells in the effector phase and antigen-specific Th17 cells cooperate to enhance Th2 cell-mediated eosinophil recruitment into the airways.
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