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

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。

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.