| Project/Area Number |
13670339
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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 |
Hygiene
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| Research Institution | Kagoshima University |
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Principal Investigator |
XU Baohui Kagoshima University, Faculty of Medicine, Research Associate, 医学部, 助手 (00264408)
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| Co-Investigator(Kenkyū-buntansha) |
AOYAMA Kohji Kagoshima University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (70117472)
TAKEUCHI Toru Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (00188161)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Lung mucosal immune tissue / Allergic asthma / Allergen / Chemokine / SLC / 喘息 / 気管支付属リンパ組織 / 肺粘膜免疫 / 二次リンパ組織ケモカイン / マウス |
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| Research Abstract |
In this project, we have investigated the development of lung mucosal lymphoid tissue (BALT) and its involvement in allergic asthma in view of lymphocyte homing. First, we have demonstrated that lymphocyte homing to BALT was mediated by L-selectin/PNAd, α4β1 integrin/VCAM-1 and LFA-1 cell adhesion pathways. In particular, the high involvement of integrin/VCAM-1 in lymphocyte homing is unique to secondary lymphoid tissue and is share a common pathway with lymphocyte infiltration in inflamed lung. Second, we have studied the role of chemokine CCR7 ligands (SLC and MIP-3β) in lymphocyte homing to BALT. We demonstrated the expression of SLC and MIP-3β in BALT using immunostaining and LCM-based RT-PCR. We further showed that lymphocyte desensitized with SLC or MIP-3β significantly depressed homing to BALT and that lymphocyte homing to BALT was largely impaired in mice lacking SLC and MIP-3β. Third, we studied the role of CCR7 ligands in the development of allergic asthma. Compared with wild type mice, we found that allergic asthma was enhanced in mice lacking SLC and MIP-3β as indicated by increased eosinophils and lymphocytes in BAL, high total IgE and antigen-specific IgE and Th2 cytokines (IL-4 and IL-13) in inflamed lung. Fourth, we compared the development of allergic asthma between wild type and NF-κB-inducing kinase mutant mice (lacking lung mucosal lymphoid tissues). We found that allergic asthma was significantly inhibited in NF- NF-κB-inducing kinase mutant mice B-inducing kinase mutant mice as measured by decrease in eosinophils and lymphocytes in BAF, low total and antigen-specific serum IgE, low level expression of VCAM-1 in inflamed lung vessels and decreases in memory T cells particularly α4β1 integrin positive T cells in BAF. Taken together, our research results indicate that lung mucosal lymphoid tissue plays an important role in the development of allergic asthma.
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