Investigation on the role of lung mucosal immune tissue in the development of allergic asthma

肺黏膜免疫组织在过敏性哮喘发生发展中作用的研究

• 批准号: 13670339
• 负责人: XU Baohui
• 金额: $ 2.43万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670339/
• 关键词: 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

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.

在这个项目中，我们研究了肺粘膜淋巴组织（BALT）的发展及其参与过敏性哮喘的发展。首先，我们已经证明，淋巴细胞归巢是由L-选择蛋白/PNAD，α4β1整合素/VCAM-1和LFA-1细胞粘附途径介导的。特别是，整联蛋白/VCAM-1在淋巴细胞寄养中的高参与是次级淋巴组织独有的，并且在发炎的肺中具有淋巴细胞浸润的共同途径。其次，我们研究了趋化因子CCR7配体（SLC和MIP-3β）在淋巴细胞归巢中的作用。我们使用免疫染色和基于LCM的RT-PCR证明了SLC和MIP-3β在BALT中的表达。我们进一步表明，用SLC或MIP-3β脱敏的淋巴细胞显着降低了对Balt的降低，并且缺乏SLC和MIP-3β的小鼠，淋巴细胞归巢为Balt。第三，我们研究了CCR7配体在过敏性哮喘发展中的作用。与野生型小鼠相比，我们发现缺乏SLC和MIP-3β的小鼠增强了过敏性哮喘，如BAL，高总IgE和抗原特异性IGE和Th2细胞因子（IL-4和IL-4和IL-13）的嗜酸性粒细胞和淋巴细胞增加所表明的那样。第四，我们比较了野生型和NF-κB诱导的激酶突变小鼠之间过敏性哮喘的发展（缺乏肺粘膜淋巴组织）。我们发现，在NF-NF-NF-κB诱导的激酶突变小鼠B诱导的激酶突变小鼠中，过敏性哮喘受到显着抑制，如通过嗜酸性粒细胞和BAF的降低和淋巴细胞的降低所测量的，在总和和抗原特异性血清中的低水平表达，在vCAM-1的低水平表达中，均降低了lunges lumperα的均体内them-nf-nf-κB，在BAF中的降低和淋巴细胞中的淋巴细胞中，均在低水平中降低了。在巴夫。综上所述，我们的研究结果表明，肺粘膜淋巴组织在过敏性哮喘的发展中起着重要作用。

项目成果

胥 宝会他: "BALTへのリンパ球ホーミングにおけるSLCの役割"日本衛生学雑誌. 56・増刊. 231-231 (2001)

Houkai Takara 等人：“SLC 在淋巴细胞归巢至 BALT 中的作用”，日本卫生杂志 56，特别版（2001 年）。

Xu BH, Bulfone-Paus S, Aoyama K, Yu S, Huang PX, Morimoto K, Takeuchi T: "Role of Fas/Fas ligand-mediated apoptosis in murine contact hypersensitivity"International Immunopharmacology. (In press). (2003)

Xu BH、Bulfone-Paus S、Aoyama K、Yu S、Huang PX、Morimoto K、Takeuchi T：“Fas/Fas配体介导的细胞凋亡在小鼠接触性超敏反应中的作用”国际免疫药理学。

Xu BH, Bulfone-Paus S, Aoyama K, Yu S, Huang PX, Morimoto K, Takeuchi T.: "Role of Fas/Fas ligand-mediated apoptosis in murine contact hypersensitivity"International Immunopharmacology. in press. (2003)

Xu BH、Bulfone-Paus S、Aoyama K、Yu S、Huang PX、Morimoto K、Takeuchi T.：“Fas/Fas 配体介导的细胞凋亡在小鼠接触性超敏反应中的作用”国际免疫药理学。

Xu BH, Wagner N, Pham LN, Magno V, Shan ZY, Butcher EC, Michie SA: "Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin/PNAd, α4β1 integrin/VCAM-1 and LFA-1 pathways"Journal of Experimental Medicine. 197 (10). 1255-12

Xu BH、Wagner N、Pham LN、Magno V、Shan ZY、Butcher EC、Michie SA：“淋巴细胞归巢至支气管相关淋巴组织 (BALT) 是由 L-选择素/PNAd、α4β1 整合素/VCAM-1 和 LFA 介导的-1途径”实验医学杂志.197(10).1255-12

Mikulowska-Mennis A, Xu BH, Berberian JM, Michie SA: "Lymphocyte migration to inflamed lacrimal glands is mediated by vascular cell adhesion molecule-1/α4β1 integrin, peripheral node addressin/L-selectin, and lymphocyte funtion-associated antigen-1 adhesi

Mikulowska-Mennis A、Xu BH、Berberian JM、Michie SA：“淋巴细胞向发炎泪腺的迁移是由血管细胞粘附分子 1/α4β1 整联蛋白、外周节点地址素/L-选择素和淋巴细胞功能相关抗原 1 介导的粘附