天疱疮是一器官特异性自身免疫性大疱性皮肤病，循环中特异性自身抗体发挥了重要的致病作用，传统长期大剂量糖皮质激素等免疫抑制剂的治疗给患者带来很多不良反应。我们在临床上尝试外用糖皮质激素治疗局部皮损，获得了明显的疗效，可促进患者症状的缓解，减少长期系统激素的用量，提高安全性。为了探明天疱疮皮损局部的免疫学机制，本项目在前期工作的基础上，进行了序贯性研究，针对皮损局部T、B细胞的表型和功能进行研究，揭示了局部B细胞处于活化状态，并可产生特异性抗体，又进一步阐明IL-17在B细胞产生抗体过程中的调节机制。通过本研究，我们将提出在天疱疮的免疫病理状态下，局部B细胞通过产生特异性抗体促进或加重了患者皮损的形成；而局部介导炎症反应的IL-17则对此过程有进一步的促进作用。本研究首次确立了皮损局部B细胞产生抗体的致病作用，丰富了天疱疮皮损的形成机制，亦为外用糖皮质激素治疗天疱疮提供了理论依据和实验基础。

Pemphigus is an organ-specific autoimmune bullous disease. The circulating antibody plays an important role in the disease. The traditional treatment is systemic steroids which will bring severe side effects. Clinically, we found that the patients got good response on topical steroids application for preventing the side effects from systemic glucocorticoid. To explore the mechanism for the local immune response, we continue the research on pemphigus based on our previous study. We will focus on the local B cells to see whether and how they produce the specific anti-Desmoglein antibody, further to detect the regulatory role of IL-17. We try to conclude that local B cells could be activated and have the ability to produce the specific antibody. Meanwhile, the local inflammation could aggravate the lesions as well. Our research will provide the new evidence on the formation of skin lesions in the disease and reveal the role of IL-17 in this process. It also strengthens the theoretic conception for the topical treatment in pemphigus and further in bullous diseases as well.