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

TL;DR

This study reveals how epithelial pyroptosis activates harmful immune cells to worsen oral inflammation and introduces a new database for research.

Contribution

The study identifies a novel mechanism involving TREM1+ macrophages and introduces ORGUAMIA, a spatiotemporal database for mucosal immune research.

Findings

Epithelial pyroptosis activates TREM1+ macrophages, which in turn stimulate Th17 cells to drive oral mucosal inflammation.

The study established ORGUAMIA, an online database to explore inflammatory roles in chronic digestive tract disorders.

Interleukin-1β was identified as a key mediator in the activation of pathogenic Th17 cells by TREM1+ macrophages.

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.

Figures