Epithelial pyroptosis-induced TREM1+ macrophages activate Th17 cells to accelerate oral mucosal inflammation
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)<sup>+</sup> 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<sup>+</sup> macrophages in chronic digestive tract disorders. In summary, this study highlights the role of epithelial pyroptosis-induced TREM1<sup>+</sup> macrophages accelerating mucosal epithelial inflammation and offers ORGUAMIA as a tool for researchers using scRNA-seq and spatial transcriptome without technological barriers.
Authors
- Maofeng Qing (ORCID: https://orcid.org/0000-0001-7829-5564)
- Hongxia Dan (ORCID: https://orcid.org/0000-0002-9765-0012)
- Qianhui Shang (ORCID: https://orcid.org/0000-0003-1929-9930)
- Xiaoyu Huang (ORCID: https://orcid.org/0009-0003-1552-0295)
- Yu Zhou (ORCID: https://orcid.org/0000-0002-5276-1616)
- Hao Xu (ORCID: https://orcid.org/0000-0002-5665-0139)
- Dunfang Zhang (ORCID: https://orcid.org/0000-0001-7545-9930)
- Xin Zeng (ORCID: https://orcid.org/0000-0002-4180-3366)
- Ziyuan Wang (ORCID: https://orcid.org/0000-0002-2632-2337)
- Jiaxin Liu (ORCID: https://orcid.org/0009-0006-5232-3997)
- Weiqi Li (ORCID: https://orcid.org/0000-0001-6141-1864)
- Dan Yang (ORCID: https://orcid.org/0000-0002-7845-9159)
- Hao Cheng (ORCID: https://orcid.org/0000-0003-1282-3496)
- Jiakuan Peng
- Qianming Chen (ORCID: https://orcid.org/0000-0001-8255-7635)
Institutions
- North Sichuan Medical University (CN)
- Dalian Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Sichuan University (CN)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Zhejiang University Medical College Affiliated Stomatological Hospital (CN)
- Stomatology Hospital (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Cell Death Discovery
- Published
- 2025-11-29
- DOI
- https://doi.org/10.1038/s41420-025-02853-7
- Primary Topic
- Inflammation biomarkers and pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- West China Hospital, Sichuan University