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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)\n                    <jats:sup>+<\/jats:sup>\n                    macrophages activated pathogenic T helper cell 17 via interleukin-1\u03b2, 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\n                    <jats:sup>+<\/jats:sup>\n                    macrophages in chronic digestive tract disorders. In summary, this study highlights the role of epithelial pyroptosis-induced TREM1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages accelerating mucosal epithelial inflammation and offers ORGUAMIA as a tool for researchers using scRNA-seq and spatial transcriptome without technological barriers.\n                  <\/jats:p>","DOI":"10.1038\/s41420-025-02853-7","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T06:25:37Z","timestamp":1764397537000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Epithelial pyroptosis-induced TREM1+ macrophages activate Th17 cells to accelerate oral mucosal inflammation"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1929-9930","authenticated-orcid":false,"given":"Qianhui","family":"Shang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiakuan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maofeng","family":"Qing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Dan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4180-3366","authenticated-orcid":false,"given":"Xin","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7545-9930","authenticated-orcid":false,"given":"Dunfang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5665-0139","authenticated-orcid":false,"given":"Hao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8255-7635","authenticated-orcid":false,"given":"Qianming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"2853_CR1","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/s41577-020-00488-6","volume":"21","author":"G Hajishengallis","year":"2021","unstructured":"Hajishengallis G, Chavakis T. 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