| Project/Area Number |
14570549
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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 |
Respiratory organ internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
TACHIBANA Isao Osaka University, Department of Molecular Medicine, Assistant Professor, 医学系研究科, 助手 (60324761)
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| Co-Investigator(Kenkyū-buntansha) |
GOYA Sho Osaka University Hospital, Department of Respiratory Medicine, Medical staff, 医学部附属病院, 医員(臨床研究)
OSAKI Tadashi Osaka University, Department of Molecular Medicine, Assistant Professor, 医学系研究科, 助手 (50324778)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | semaphorin / CD100 / gene targeting / allergic airway inflammation / airway hyperreactivity / Th2 response / tolerance / 免疫寛容 / 気道過敏症 |
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| Research Abstract |
CD100, the first semaphorin that has been shown to function in the immune system, enhances various immune responses, including anti body production, T cell priming and dendritic cell maturation. We investigated the involvement of CD100 in the pathogenesis of allergic airway inflammation by employing mutant mice lacking CD100.
METHODS: To induce allergic responses to airborne antigen, both wild-type BALB/c mice and CD100 deficient mice on BALB/c background were sensitized with intraperitoneal injection of chicken ovalbumin (OVA) in Alum and then were challenged by inhalation of OVA.
RESULTS: Actively immunized CD100 deficient mice exhibited exaggerated allergic responses to aerosolized OVA, which include increased serum OVA-specific IgE, marked airspace eosinophilia and enhanced airway hyperresponsiveness to methacholine, compared with wild-type animals. When cultured with OVA, bronchial lymph node cells isolated from CD100 deficient mice after antigen challenge paradoxically secreted smaller amounts of Th2 cytokines (IL-4, 5 and 13) than those from wild-type mice. On one hand, the production of an immunosuppressive cytokine (IL-b) also decreased in the former group.
It is known that intranasal administration of OVA prior to immunization induces unresponsiveness to the antigen. This phenomenon called (nasal tolerance) did not occurred in CD 100 deficient mice. CONCLUSION: In CD100 deficient mice, although the ability to drive Th2 immunity is impaired, a failure of the regulatory machinery, which induces the mucosal tolerance by nature, is supposed to lead to an excess of allergic pulmonary inflammation.
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