唾液腺上皮细胞异常抗原递呈是舍格伦综合征（SS）发病的始动因素之一，其原因和机制尚不明确。我们以往研究发现固有免疫信号TLR9在SS患者腺上皮细胞中异常高表达，并发现TLR9促进唾液腺细胞自噬性降解和MHC-II型分子合成，诱导其异常抗原递呈。通过芯片分析及筛选，我们发现去泛素酶Usp13可能通过对AMPK和CIITA的泛素化调控，参与TLR9介导的唾液腺上皮细胞异常抗原递呈。因此，本项目拟在明确TLR9调控Usp13的基础上，通过功能验证确认Usp13在TLR9介导异常抗原递呈中的作用。进一步通过Co-IP、质谱测序等方法，明确Usp13参与细胞前期自噬性抗原摄取及后期MHC-II型分子转换的分子机制。最后通过SS相关模型鼠的构建，探讨靶向Usp13泛素化治疗SS的潜在优势。本项目的开展有助于完善SS发病机制，为后续SS诊断及治疗提供理论依据和实践基础。

Abnormal antigen-presentation in salivary gland epithelial cells are initiating factors of Sjogren’s syndrome(SS), but the mechanism on how the abnormal antigen-presentation initiated remains unclear. Our previous research identified an over-expression of TLR9 in salivary gland epithelial cells of SS patients. Further studies identified that TLR9 promoted autophagic degradation and class-II MHC synthesis, indicating a strengthened antigen-presentation in salivary gland epithelial cells. Utilized by high-throughput analysis and filter assays, we discovered that the Deubiquitinase USP13 might acted as a key regulator in TLR9-induced antigen presentation in salivary gland epithelial cells. In our experiments, we identified that Usp13 might regulate the ubiquitin levels of AMPK, the important sensor-like protein of autophagy, and CIITA, the transcriptional factor of class-II MHC. Therefore, this study aimed to identify the role of TLR9/Usp13 signaling axis in antigen-presentation process, and further explore the molecular mechanism of Usp13 in salivary gland epithelial cells and SS pathogenesis. This study aims at strong scientific evidence for improving the disease diagnosis and drug therapy.