Clarification of the molecular and cellular mechanisms of central and peripheral tolerance to pemphigus autoantigen

阐明中枢和外周天疱疮自身抗原耐受的分子和细胞机制

• 批准号: 21229014
• 负责人: AMAGAI Masayuki
• 金额: $ 134.62万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009-05-11 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21229014/
• 关键词: 皮膚免疫学; 免疫寛容; 自己免疫; モデルマウス; 樹状細胞; 天疱瘡; Interface Dermatitis; 乾癬; デスモグレイン; 気管支炎; 免役寛容

The purpose of this study is to clarify the pathogenic roles of T cells specific for desmoglein 3 (Dsg3), the autoimmune target antigen in pemphigus vulgaris, and the mechanisms of tolerance to Dsg3 in vivo. Dsg3-specific T cells were able to induce not only pemphigus vulgaris, but also unexpectedly interface dermatitis and psoriasis-like skin lesions. This model provides an important tool to dissect the pathophysiological mechanisms for interface dermatitis as experimental autoimmune dermatitis (EAD). While Dsg3-specific T cells are usually deleted in the thymus (central tolerance), it was demonstrated that these T cells could be deleted solely in the periphery (peripheral tolerance) when thymic epithelial cells did not express Dsg3. Further dissection of the mechanisms for peripheral tolerance will lead us to develop a novel therapeutic strategy for antigen-specific immune suppression.

本研究旨在阐明寻常型天疱疮自身免疫靶抗原桥粒芯糖蛋白3（Dsg3）特异性T细胞的致病作用以及Dsg3耐受的体内机制。Dsg3特异性T细胞不仅能够诱导寻常型天疱疮，而且还能够意外地诱导界面皮炎和银屑病样皮肤病变。该模型为研究实验性自身免疫性皮炎（EAD）的病理生理机制提供了重要工具。虽然Dsg3特异性T细胞通常在胸腺中缺失（中枢耐受性），但已证明当胸腺上皮细胞不表达Dsg3时，这些T细胞可仅在外周中缺失（外周耐受性）。对外周免疫耐受机制的进一步研究将有助于我们开发一种新的抗原特异性免疫抑制治疗策略。

项目成果

Investigation of the tight junction barrier in hair follicles and sebaceous glands

毛囊和皮脂腺紧密连接屏障的研究

• 发表时间: 2011
• 作者: Shin'ichi Arakawa;Tetsuya Takine;Masayuki Murata;Yui Sasaki;大石敏之;Kubo A
• 通讯作者: Kubo A

Asian Skin and Skin Diseases～Special book of the 22nd World Congress of Dermatology～

亚洲皮肤及皮肤病～第22届世界皮肤病学大会特刊～

• 发表时间: 2011
• 作者: Chan;P.T.
• 通讯作者: P.T.

Mechanisms of epidermal barrier and its dysfunction in atopic diseases

特应性疾病中表皮屏障及其功能障碍的机制

• 发表时间: 2011
• 作者: M.Naito;K.Ebihara;M.Mukoyama;K.Hosoda;K.Nakao;et al;Katsuro Inoue;稲生 大輔;Amagai M
• 通讯作者: Amagai M

Langerhans cells play an essential role in inducing protective humoral immune response subsequent to antigen uptake through tight junctions

朗格汉斯细胞在通过紧密连接摄取抗原后诱导保护性体液免疫反应中发挥重要作用

• 发表时间: 2011
• 作者: N.Yamada;K.Ebihara;K.Hosoda;K.Nakao;et al;Ouchi T
• 通讯作者: Ouchi T

Langerhans cells confer pre-emptive immunity via antigen capture through tight junctions in experimental staphylococcal scalded skin syndrome

朗格汉斯细胞通过紧密连接捕获抗原，在实验性葡萄球菌烫伤皮肤综合征中提供先发性免疫

• 发表时间: 2011
• 作者: Adachi S.;et al;武藤誠;Nagao K
• 通讯作者: Nagao K