Highlights of Tuft Cells in Mouse and Human Salivary Glands

Tuft cells (TCs) are rare chemosensory epithelial cells that regulate mucosal homeostasis in several organs, but their role in salivary glands (SGs) remains unclear. This study investigated TC features in both mouse and human SGs. In mouse samples, transmission electron microscopy (TEM), histological analysis, bulk RNA-sequencing and proteomic analyses were performed on submandibular glands (SMGs) from female and male C57BL/6J (wild-type) and C57BL/6J-Pou2f3-/- mice, which lack TCs. Moreover, human minor SG biopsies were evaluated by immunostaining and Poisson regression to identify clinical, serological, and histopathological features correlated with TC abundance. TEM analysis confirmed conserved TC ultrastructure—apical microvilli, a tubulovesicular system, and cytospinules—in both female and male mouse SMGs. Moreover, TC loss was associated with sex-specific transcriptional remodeling (1742 differentially expressed genes in females versus 175 in males), morphological alterations and sex-specific saliva proteomic remodeling. In human minor SG biopsies, TC counts were correlated with salivary flow, serological and histopathology features. In summary, these findings suggest that TCs are regulators of epithelial integrity and potential biomarkers of SG dysfunction.