Gene signature for MCTC activation shown through transcriptome analysis of MCTCs in CRSwNP

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a Th2 disease characterized by heterogeneous mast cell hyperplasia. We previously characterized transcriptional differences between MCT and MCTC phenotypes in nasal polyps. Whether and how the expanded MCTCs in CRSwNP differ from the constitutively present MCTCs remains poorly understood. We used RNAseq to compare MCTCs in CRSwNP to those in CRSsNP from control donors. We identified differentially regulated sets of cytokines, pro-inflammatory mediators, and cell receptors associated with MCTCs in each disease state. To better understand the signals driving specific gene expression patterns, we used a series of gene signatures generated through in vitro mast cell stimulation. We identified an activation cassette enriched in CRSwNP consisting of cytokines (IL13, CSF), chemokines (CCL2, CXCL8), and cell surface proteins including transcripts like IL2RA, which codes for CD25, a canonical marker of clonally expanded mast cells systemic in mastocytosis. Thus, our analysis provides novel insight into the difference between MCTCs in CRSwNP and CRSsNP, indicating that MCTCs in nasal polyps have an activated phenotype.