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

Area of Science:

• Immunology
• Rhinology
• Molecular Biology

Background:

• Chronic rhinosinusitis with nasal polyps (CRSwNP) is a Th2-mediated disease with mast cell hyperplasia.
• Subepithelial mast cells co-expressing tryptase and chymase (MC_TCs) are present in both CRSwNP and CRS without nasal polyposis (CRSsNP).
• Differences in MC_TCs between these disease states are not well understood.

Purpose of the Study:

• To compare MC_TCs in CRSwNP and CRSsNP using transcriptomics and flow cytometry.
• To identify differentially expressed genes and pathways in MC_TCs across disease states.

Main Methods:

• MC_TCs were isolated from CRSwNP and CRSsNP patient samples.
• RNA sequencing (RNAseq) was performed to analyze gene expression.
• Flow cytometry and ex-vivo stimulated primary mast cells were used for validation.

Main Results:

• MC_TC concentration was significantly higher in CRSwNP patients.
• CRSwNP MC_TCs showed enrichment in activation-associated pathways, including differential expression of pro-inflammatory mediators and IL2RA.
• CD25 (IL2RA) was significantly upregulated on the surface of MC_TCs in CRSwNP.

Conclusions:

• MC_TCs in CRSwNP exhibit an activated transcriptional profile.
• IL2RA and its cell-surface marker CD25 may serve as indicators of activated MC_TCs in allergic diseases like CRSwNP.