寻常型天疱疮(PV)发病机制与角质细胞粘附性密切相关，桥粒芯蛋白Dsg3内吞会导致角质细胞粘附性丧失，促进PV的发生。免疫负调控因子白介素(IL)-37能调节多种自身免疫性疾病和皮肤病的发生，但其在PV中的作用尚不明确。前期工作发现IL-37在PV患者血清中含量增加，重组IL-37蛋白能增加角质细胞的粘附性，抑制Dsg3内吞；蛋白内吞调节分子小窝蛋白(Cav)-1在PV病损组织和细胞中表达均下调，而IL-37可上调其表达。我们提出“IL-37通过上调Cav-1抑制 Dsg3内吞，从而抑制PV发生”的假设。①分析IL-37在PV患者血清、皮损部位、单个核细胞等的表达及临床意义；②利用免疫学和分子生物学技术，阐明IL-37调控角质细胞Dsg3内吞的作用机制；③建立PV小鼠模型，验证IL-37在体内影响PV发生和进展的作用。揭示IL-37在PV中的作用和机制，为PV的治疗提供新的思路和方法。

Pemphigus vulgaris (PV) 's pathogenesis is closely related to keratinocyte adhesion.Desmoglein (Dsg) 3 endocytosis induces a loss of keratinocyte adhesion and promotes the development of pemphigus vulgaris (PV). Studies have shown that interleukin (IL)-37, a negative regulator of immunity, can modulate the pathogenesis of multiple autoimmune diseases and skin diseases. However, the role of IL-37 in PV remains to be clarified. Our previous work revealed that IL-37 expression was elevated in the serum of PV patients; recombinant IL-37 protein could increase the adhesion of keratinocytes and suppress Dsg3 endocytosis. Caveolin (Cav)-1, an important regulator of protein endocytosis, was downregulated in lesioned-tissues and cells of PV, while it was upregulated by IL-37. Therefore, we propose that “IL-37 suppresses Dsg3 endocytosis via upregulating Cav-1 expression and attenuates the development of PV”. The present project intends to: (1) analyze IL-37 expression in the serum, cutaneous lesions and mononuclear cells of PV patients as well as their clinical significance; (2) clarify the mechanism of IL-37 in regulating Dsg3 endocytosis in keratinocytes by using immunological and molecular biology techniques; (3) verify the role of IL-37 in the development and progress of PV in vivo by the establishment of a PV mouse model. This project will uncover the role and mechanism of IL-37 in PV and may provide novel insight and methods for PV therapy.