| Project/Area Number |
16390288
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
MAZUDA Osamu Kyoto Prefectural University of Medicine, Graduate School of Medicine, MD, PhD, Associate Professor, 医学研究科, 助教授 (00271164)
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| Co-Investigator(Kenkyū-buntansha) |
IMANISHI Jiro Kyoto Prefectural University of Medicine, Graduate School of Medicine, MD., PhD, Professor, 医学研究科, 教授 (40112510)
YOSHIKAWA Toshikazu Kyoto Prefectural University of Medicine, Graduate School of Medicine, MD., PhD, Professor, 医学研究科, 教授 (90158410)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2005: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | Allergy / Cytokine / Molecular therapy / Immune response / IgE / IL-21 / 遺伝子治療 / 分子制御 / 免疫療法 |
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| Research Abstract |
Conventional treatments for allergic diseases include antagonization of chemical mediators and immunosuppression, while therapeutic approaches to directly suppress IgE have not been succeeded. IL-21 reportedly inhibit IgE production from B cells in culture, but in vivo effect of IL-21 on IgE synthesis remains unrevealed. The study aims at investigating the mechanisms of IL-21-mediated regulation of allergic reactions as well as devising novel therapeutic intervention to control allergic diseases. Murine models of peanuts anaphylaxis and allergic rhinitis were established and they were administered with IL-21 gene or recombinant IL-21 (rIL-21) with/without nanoparticles as a carrier. Hydrodynamics-mediated delivery of IL-21 gene resulted in significant suppression of both peanuts anaphylaxis and allergic rhinitis with a remarkable decrease in serum concentration of IgE. These effects correlated with the doses of the cytokine gene. Intraperitoneal administrations with rIL-21 drastically suppressed systemic anaphylaxis in terms of the change in body temperature and anaphylaxis scores, with significant reduction of the expression level of IgH C epsilon germ line transcript in the spleen. Allergic rhinitis was also clearly ameliorated after therapeutic or prophylactic intranasal administrations with rIL-21, which significantly reduced IgE titer in the sera of the animals. When IL-21 was added to the culture of B lymphocytes obtained from murine spleens, the treatment induced significant reduction in the amount of mRNA corresponding to the IgH C epsilon germ line sequence, while Id2 was significantly induced in the B cells strongly suggesting that the IL-21 signal blocks epsilon switch recombination through the activation of Id2. The present study showed that IL-21 may provide a novel therapeutic strategy to treat allergy through inhibiting IgE production from the B cells. Id2 may be crucially involved in the suppression of IgE class switch induced by the IL-21 signaling.
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