Analysis of helper T cell subset in severe asthma for the development of new immunotherapy

分析严重哮喘中的辅助性 T 细胞亚群以开发新的免疫疗法

• 批准号: 21390255
• 负责人: NAKAJIMA Hiroshi
• 金额: $ 11.23万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390255/
• 关键词: 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

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.

哮喘是一种慢性气道炎症，其特征是嗜酸性粒细胞浸润、粘液分泌过多以及对各种刺激的气道高反应性（AHR）。这些特性主要由抗原特异性 Th2 细胞及其细胞因子（包括 IL-4、IL-5 和 IL-13）介导。此外，我们和其他人已经证明，Th17 细胞部分通过产生 IL-17A 诱导中性粒细胞气道炎症。最近，IL-22（一种 Th17 细胞衍生的细胞因子，具有促炎和抗炎特性）已被证明可以在哮喘小鼠模型的气道中检测到。然而，IL-22在调节过敏性气道炎症中的作用仍然很大程度上未知。在本研究中，我们发现IL-22是由抗原攻击时浸润在气道中的CD4^+T细胞产生的，中和IL-22 -22 效应期抗 IL-22 抗体增强了抗原诱导的嗜酸性粒细胞募集到气道中，并且鼻内施用重组 IL-22 抑制了抗原诱导的嗜酸性粒细胞募集到气道中航空公司。我们还发现抗 IL-22 抗体增强了气道中抗原诱导的 IL-25 产生，已知这可以增强气道中的 Th2 型免疫反应，并且确实联合注射抗 IL-25 抗体逆转了气道中的 Th2 型免疫反应。抗 IL-22 抗体对抗原诱导的嗜酸性粒细胞募集到气道中的增强作用。最后，我们发现在 LPS 刺激的肺上皮细胞系 MLE-15 细胞中，IL-22 抑制 IL-13 介导的 IL-25 表达增强。我们的结果表明，IL-22 部分通过抑制肺上皮细胞中 IL-25 的表达来减轻抗原诱导的气道炎症。

项目成果

Color-coded real-time cellular imaging of T lymphocyte accumulation and focus formation in mouse asthma model.

小鼠哮喘模型中 T 淋巴细胞积累和病灶形成的颜色编码实时细胞成像。

• 发表时间: 2010
• 期刊: J Allergy Clin. I m m u n o l. 125
• 作者: Hasegawa;A.;Hayashi;K.;Kishimoto;H.;Yang;M.;Tofukuji;S.;Suzuki;K.;Nakajima;H.;Hoffman;R.M.;Shirai;M.;Nakayama;T.
• 通讯作者: T.

Role of Th2 Cells in IgG4-Related Lacrimal Gland Enlargement

• DOI: 10.1159/000312125
• 发表时间: 2010-01-01
• 期刊: INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
• 影响因子: 2.8
• 作者: Kanari, Hiroko;Kagami, Shin-ichiro;Nakajima, Hiroshi
• 通讯作者: Nakajima, Hiroshi

A functional polymorphism in B and T lymphocyte attenuator is associated with susceptibility to rheumatoid arthritis.

• DOI: 10.1155/2011/305656
• 发表时间: 2011
• 期刊: Clinical & developmental immunology
• 作者: Oki M;Watanabe N;Owada T;Oya Y;Ikeda K;Saito Y;Matsumura R;Seto Y;Iwamoto I;Nakajima H
• 通讯作者: Nakajima H

IL-25とアレルギー

IL-25 和过敏

• 发表时间: 2010
• 作者: 片村嘉男;相方浩;石田友希;阿座上隆広;河岡友和;高木慎太郎;脇浩司;平松憲;川上由育;高橋祥一;茶山一彰;中島裕史
• 通讯作者: 中島裕史

IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation

• DOI: 10.1016/j.jaci.2011.06.018
• 发表时间: 2011-11-01
• 期刊: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
• 影响因子: 14.2
• 作者: Takahashi, Kentaro;Hirose, Koichi;Nakajima, Hiroshi
• 通讯作者: Nakajima, Hiroshi