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.

哮喘是以嗜酸性粒细胞浸润、粘液高分泌和对多种刺激的气道高反应性（AHR）为特征的慢性气道炎症。这些特征主要由抗原特异性Th 2细胞及其细胞因子（包括IL-4、IL-5和IL-13）介导。此外，我们和其他人已经表明，Th 17细胞部分通过产生IL-17 A诱导嗜中性粒细胞气道炎症。最近，IL-22，一种具有促炎和抗炎特性的Th 17细胞衍生的细胞因子，已显示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不清楚，在这项研究中，我们发现IL-22是由抗原激发时气道中浸润的CD 4 ^+ T细胞产生的，在效应期抗IL-22抗体对IL-22的中和作用增强了抗原诱导的嗜酸性粒细胞向气道的募集，并且鼻内施用重组IL-22抑制抗原诱导的嗜酸性粒细胞募集到气道中。我们还发现，抗IL-22抗体增强气道中抗原诱导的IL-25产生，已知其增强气道中的Th 2型免疫应答，并且实际上共注射抗IL-25抗体逆转了抗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IL-22抑制IL-13介导的LPS刺激的肺上皮细胞系MLE-15细胞中IL-25表达的增强。我们的研究结果表明，IL-22减弱抗原诱导的气道炎症，部分通过抑制肺上皮细胞中IL-25的表达。

项目成果

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

ヘルパーT細胞とアレルギー性炎症

辅助T细胞和过敏性炎症

• 发表时间: 2009
• 作者: 樂木宏実;中島裕史
• 通讯作者: 中島裕史

Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice

• DOI: 10.1093/intimm/dxr017
• 发表时间: 2011-05-01
• 期刊: INTERNATIONAL IMMUNOLOGY
• 影响因子: 4.4
• 作者: Oya, Yoshihiro;Watanabe, Norihiko;Nakajima, Hiroshi
• 通讯作者: Nakajima, Hiroshi

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

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