Single-Cell Transcriptomic Atlas of Gingival Mucosa in Type 2 Diabetes
Qi Wang, Weiping Lin, Xuedong Zhou, Kai Lei, Ruoshi Xu, X. Zhang, Qiuchan Xiong, Rui Sheng, Wenqiang Song, W. Liu, Qi Wang, Quan Yuan
Abstract
The oral gingival barrier is a constantly stimulated and dynamic environment where homeostasis is often disrupted, resulting in inflammatory periodontal diseases. Type 2 diabetes (T2D) has been reported to be associated with gingival barrier dysfunction, but the effect and underlying mechanism are inconclusive. Herein, we performed single-cell RNA sequencing (scRNA-seq) of gingiva from leptin receptor-deficient mice ( db/db) to examine the gingival heterogeneity in the context of T2D. Periodontal health of control mice is characterized by populations of Krt14 + -expressing epithelial cells and Col1a1 + -fibroblasts mediating immune homeostasis primarily through the enrichment of innate lymphoid cells. The db/db gingiva exhibited decreased epithelial/stromal ratio and dysfunctional barrier. We further observed stromal, particularly fibroblast immune hyperresponsiveness, linked to the recruitment of myeloid-derived cells at the db/db gingiva. Both scRNA-seq and histological analysis suggested the inflammatory signaling between fibroblasts and neutrophils as a potential driver of diabetes-induced periodontal damage. Notably, the “immune-like” stromal cells were wired toward the induction of gingival IL-17A hyperresponsiveness in db/db mice. Our work reveals that the “immune-like” fibroblasts with transcriptional diversity are involved in the innate immune homeostasis at the diabetic gingiva. It highlights a potentially significant role of these cell types in its pathogenesis.