Epithelial pyroptosis-induced TREM1+ macrophages activate Th17 cells to accelerate oral mucosal inflammation

作者：Qianhui Shang, Ziyuan Wang, Jiakuan Peng, Dan Yang, Weiqi Li, Xiaoyu Huang, Maofeng Qing, Hao Cheng, Jiaxin Liu, Hongxia Dan, Xin Zeng, Yu Zhou, Dunfang Zhang, Hao Xu, Qianming Chen · 发表于：Cell Death Discovery · 年份：2025 · DOI：10.1038/s41420-025-02853-7 · 被引用次数：1 · 研究领域：Inflammation biomarkers and pathways、Inflammasome and immune disorders、Oral microbiology and periodontitis research

Abstract Chronic inflammation of the oral mucosa could affect daily living and even threaten systemic health. Unlike periodontitis, oral lichen planus, a common oral chronic inflammatory disease, has diverse clinical manifestations and can progress to malignancy. Hence, this study aimed to investigate the mechanism of oral chronic inflammation using single-cell RNA sequencing (scRNA-seq), spatial transcriptome, a large clinical follow-up cohort with bulk RNA sequencing, cytological experiments, and multiplex immunohistochemistry. We found that epithelial pyroptosis-induced triggering receptor expressed on myeloid cell-1 (TREM1) + macrophages activated pathogenic T helper cell 17 via interleukin-1β, to spur the inflammatory development of oral mucosal epithelium. Besides, we established a spatiotemporal interactional online database, Oral-Gut Axis Mucosal Immune Atlas (ORGUAMIA), to uncover the extensive pro-inflammatory role of epithelial pyroptosis-induced TREM1 + macrophages in chronic digestive tract disorders. In summary, this study highlights the role of epithelial pyroptosis-induced TREM1 + macrophages accelerating mucosal epithelial inflammation and offers ORGUAMIA as a tool for researchers using scRNA-seq and spatial transcriptome without technological barriers.