Unlocking mast cell diversity in human nasal polyps

Mast Cells (MCs) infiltrate the nasal polyps of patients with chronic rhinosinusitis (CRS) and the bronchial mucosa of patients with mild, moderate, and severe asthma. MCs are a significant source of IL-33-elicited Th2 cytokines in the sputum of asthmatics and upon activation generate or release high levels of mediators including tryptase, histamine, and prostaglandin D 2 . Although airway MC heterogeneity can readily identified through protease immunostaining and tissue sub-localization, the functional distinctions and developmental relationships between MC subsets remain uncertain, in part because of the lack of flow cytometric markers to distinguish them and technical difficulties in isolating MCs. Using a novel flow cytometric approach we have identified several distinct MC subsets in the nasal polyps of patients with CRS that vary in expression of FcER1, c-kit, B7, CD203 and chymase. Nasal polyp MCs were further characterized through unbiased single cell RNA sequencing, revealing heterogeneity within the MC population and providing novel insight into transcriptional differences between these subsets.