CD25 expression marks an activated mast cell population in human nasal polyposis

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a T_H2 disease characterized by heterogeneous mast cell hyperplasia. We previously used transcriptomics to identify discrete gene expression linked with intraepithelial mast cells expressing tryptase alone (MC_Ts), subepithelial mast cells coexpressing tryptase and chymase (MC_TCs), and immature mast cells in CRSwNP. Although MC_TCs were the only subset consistently observed in both CRSwNP and chronic rhinosinusitis without nasal polyps (CRSsNP), the degree to which they differ across disease states remains unexplored.

We sought to use transcriptomics and flow cytometry to compare MC_TCs in CRSwNP with those in CRSsNP.

MC_TCs were flow-sorted from CRSwNP and CRSsNP samples for RNA-sequencing analysis to identify differentially expressed genes and pathways across disease states. In silico observations were validated using flow cytometry on cryopreserved tissue samples from CRSwNP and CRSsNP and RNA sequencing of stimulated ex vivo-differentiated MCs.

We found a significant increase in MC_TC concentrations in CRSwNP donors, which were enriched for activation-associated pathways linked with differential expression of transcripts encoding proinflammatory mediators and cell receptors, including IL2RA. Validation studies highlighted significant cell surface expression of CD25 on MC_TCs in CRSwNP. Ex vivo-stimulated primary MCs upregulated IL2RA in response to IL-33 stimulus.

Our data show that MC_TCs in CRSwNP exhibit an activated transcriptional phenotype with expression of transcripts encoding proinflammatory mediators and IL2RA. Moreover, the CD25 upregulation on MC_TCs in CRSwNP suggests its potential to serve as an in vivo marker of activated MC_TCs during allergic disease.