ScRNA-Seq Analysis of Tongue Tissues in Chronic Hyperplastic Candidiasis

Chronic hyperplastic candidiasis (CHC) is a rare but severe subtype of oral candidiasis distinguished by its potential malignant transformation and suboptimal response to antifungal therapies. However, the cells and mechanisms that play key roles in this process remain unclear. Therefore, we performed the first single-cell RNA sequencing (scRNA-seq) analysis of CHC-affected tongue tissues to reveal the microenvironmental changes and immunological etiology of CHC. First, the features of CHC lesions manifesting as thickening and hardening nodular lesions, including their pathological and microbiological characteristics, were elucidated. Then, a comprehensive cellular atlas and distinct immune landscape in CHC compared with healthy tissues were characterized using scRNA-seq, highlighting significant modifications in the cell number and functionality of fibroblasts and T/NK cells. Importantly, the central role of fibroblasts in cell-cell interactions in CHC was hinted, and possible ligand-receptor pairs mainly associated with inflammation and carcinogenesis were identified. Moreover, it was revealed that significant functional activation of fibroblasts, related to the activation of the epithelial-mesenchymal transition pathways and increased expression of collagen I, matrix metalloproteinase 1 (MMP1), and MMP2, could be a hallmark of CHC, correlating with CHC's clinical characteristics of tongue hardening and intense inflammation. Notably, there is sequencing evidence of the recruitment of CD8