Kuang Shuhong, Yang Jiayu, Shen Zongshan, Xia Juan, Lin Zhengmei
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510000, China.
Int J Mol Sci. 2024 Dec 10;25(24):13255. doi: 10.3390/ijms252413255.
Mucosal immunity plays a critical role in the pathogenesis of inflammatory immune diseases. This study leverages single-cell RNA sequencing, spatial transcriptomics, and spatial proteomics to compare the cellular mechanisms involved in periodontitis between humans and mice, aiming to develop precise strategies to protect the gingival mucosal barrier. We identified key conserved and divergent features in cellular landscapes and transcriptional profiles across the two species, underscoring the complexity of inflammatory responses and immune dynamics in periodontitis. Additionally, we revealed a novel regulatory mechanism by which epithelial cells modulate macrophage behavior and inflammation through the JAG1-Notch pathway. Validation through animal experiments revealed that JAG1 inhibition reduces inflammation in epithelial cells, mitigating periodontitis. Our findings advance the understanding of periodontal disease pathogenesis and highlight the importance of integrating human and animal model data to develop treatments aligned with human physiology, offering potential therapeutic targets for controlling inflammation and enhancing tissue regeneration.
黏膜免疫在炎症性免疫疾病的发病机制中起着关键作用。本研究利用单细胞RNA测序、空间转录组学和空间蛋白质组学来比较人类和小鼠牙周炎中涉及的细胞机制，旨在制定保护牙龈黏膜屏障的精确策略。我们在两个物种的细胞景观和转录谱中确定了关键的保守和差异特征，强调了牙周炎中炎症反应和免疫动态的复杂性。此外，我们揭示了一种新的调节机制，即上皮细胞通过JAG1-Notch途径调节巨噬细胞行为和炎症。通过动物实验验证发现，抑制JAG1可减轻上皮细胞炎症，缓解牙周炎。我们的研究结果增进了对牙周疾病发病机制的理解，并强调了整合人类和动物模型数据以开发符合人类生理的治疗方法的重要性，为控制炎症和促进组织再生提供了潜在的治疗靶点。
