Postdoctoral Research Fellow
Fellow or Postdoc
T.M. Derakhshan, E. Hollers, T.Laidlaw, J.A.Boyce, D.F.Dwyer
Mast cells (MCs) are central regulators of type 2 inflammation, including asthma and nasal polyposis, where they expand and produce factors that elicit bronchoconstriction and leukocyte infiltration. In nasal polyposis, MC expansion is partially driven by proliferation of transcriptionally immature MCs that correlates with disease severity, but the relationship between these immature MCs and the circulating MC progenitors (MCps) is unclear. To understand this, we used scRNA-seq to profile blood progenitors and MCs from donors with nasal polyposis. Through this approach, we identified MCps characterized by expression of MC-associated transcripts and a discrete surface and intracellular protein expression profile. These MCps shared transcriptional and protein expression characteristics with proliferating MCs within the nasal polyps, suggesting a link between the two. We identified a population of MCs, which primarily exhibited immature MC characteristics and circulating MCp markers and were enriched in proliferating population, indicating potential tissue MCps. While MCps had limited proliferation capacity in isolation, they robustly expanded when co-cultured with airway fibroblasts, the dominant structural cells within the tissue subepithelium. Fibroblast co-culture further enhanced subepithelial MC markers. Thus, our findings suggest a central role for airway fibroblasts in driving MC hyperplasia through eliciting MCp proliferation during type 2 inflammation.
Mast cells (MCs) are an immune cell type that are found in inflammatory diseases, such as asthma and nasal polyps. These MCs are more numerous in disease versus healthy tissue. A population of MCs that show typical characteristics of immature MCs contribute to increase in MC density. Circulating MC progenitors (MCps) are assumed to migrate to the tissue and mature to MCs, however in disease, the relationship between the circulating MCps and tissue-resident immature MCs is unclear. We used RNA sequencing technology to characterize blood progenitor cells and MCs in nasal polyps. We found circulating MCps expressing MC-associated markers. These MCps expressed proteins that were similarly expressed by some of proliferating MCs in the nasal polyps, suggesting that these proliferating MCs are tissue MCps. We also found that the circulating MCps cultured with airway fibroblasts, stromal cells that are plentiful in tissue, have a great proliferation capacity compared with MCps cultured alone. Also, fibroblasts favored MCp maturation. Therefore, our findings suggest a role for fibroblasts to enhance MCp proliferation and maturation in tissue.