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

本研究旨在阐明自身免疫靶抗原desmoglein 3 （Dsg3）特异性T细胞在寻常型天疱疮中的致病作用，以及对Dsg3的体内耐受机制。dsg3特异性T细胞不仅能够诱导寻常性天疱疮，而且意想不到地诱导界面皮炎和牛皮癣样皮肤病变。该模型为探讨界面皮炎作为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（中枢耐受）中被删除，但研究表明，当胸腺上皮细胞不表达Dsg3时，这些T细胞可以仅在周围（外周耐受）中被删除。进一步解剖外周耐受机制将引导我们开发抗原特异性免疫抑制的新治疗策略。

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.