Project 2. Basal Cell Dysplasia in Type 2 Immunopathology

Project 2 Summary/Abstract
Basal epithelial cells are the stem-like progenitor cells that give rise to all differentiated epithelial cell subsets.
In addition to their progenitor function, they produce pro-inflammatory molecules including interleukin-33 (IL-
33) and thymic stromal lymphopoietin (TSLP), implicated in the pathobiology of type 2 (T2) inflammatory
diseases such as eczema, food allergy, eosinophilic esophagitis, asthma, and nasal polyposis. Our group
recently reported that basal cells from patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) are
dysplastic, fail to differentiate into normal respiratory epithelial cells, and upregulate the capacity to generate
proinflammatory molecules. These abnormalities are associated with an aberrant metabolic program. The goal
of this research plan is to: 1) define how basal cell metabolism regulates their stem and proinflammatory
functions, 2) determine how basal cell metabolism is altered in the sinonasal tissue of patients with different
types of chronic rhinosinusitis, and 3) determine whether therapeutic inhibition of IL-4Rα will restore the
metabolic, transcriptional, and epigenetic changes seen in basal cells in a severe CRSwNP subtype, aspirin-
exacerbated respiratory disease.

Grant Number: 5U19AI095219-15
NIH Institute/Center: NIH
Principal Investigator: Nora Barrett