| Project/Area Number |
21390255
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KAGAMI Shin-ichiro 千葉大学, 医学部附属病院, 助教 (30375654)
HIROSE Koichi 千葉大学, 医学部附属病院, 講師 (90400887)
WATANABE Norihiko 千葉大学, 大学院・医学研究院, 准教授 (20375653)
SUTO Akira 千葉大学, 大学院・医学研究院, 助教 (50447306)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2011: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | 喘息 / IL-22 / IL-21 / c-Maf / T細胞 / 免疫療法 / cMaf / 気管支喘息 / アレルギー性炎症 / 気道上皮細胞 / Th17細胞 / Tfh細胞 / STAT6 / T-bet |
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| Research Abstract |
Asthma is chronic airway inflammation characterized by eosinophil infiltration, mucus hypersecretion, and airway hyperresponsiveness (AHR) to a variety of stimuli. These characteristics are mainly mediated by antigen-specific Th2 cells and their cytokines including IL-4, IL-5, and IL-13. Moreover, we and others have shown that Th17 cells induce neutrophilc airway inflammation in part through the production of IL-17A. More recently, IL-22, one of Th17 cell-derived cytokines with both proinflammatory and anti-inflammatory properties, has been shown to be detected in the airways in a murine model of asthma. However, the role of IL-22 in the regulation of allergic airway inflammation remains largely unknown.
In this study, we found that IL-22 was produced by CD4^+ T cells infiltrating in the airways upon antigen challenge, that the neutralization of IL-22 by anti-IL-22 antibody in the effector phase enhanced antigen-induced eosinophil recruitment into the airways, and that intranasal administration of recombinant IL-22 inhibited antigen-induced eosinophil recruitment into the airways. We also found that anti-IL-22 antibody enhanced antigen-induced IL-25 production in the airways, which is known to enhance Th2-type immune responses in the airways, and indeed co-injection of anti-IL-25 antibody reversed the enhancing effect of anti-IL-22 antibody on antigen-induced eosinophil recruitment into the airways. Finally, we found that IL-22 inhibited IL-13-mediated enhancement of IL-25 expression in LPS-stimulated lung epithelial cell line MLE-15 cells. Our results suggest that IL-22 attenuates antigen-induced airway inflammation in part by inhibiting the expression of IL-25 in lung epithelial cells.
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