STAT6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis and Asthma, A Model of Unified Airway Disease

Authors

Hua Sun
Ashish Damania
Megan L Mair
Eniola Otukoya
Yi-Dong Li
Katherine Polsky
Yuying Zeng
Jeremiah A Alt
Martin J Citardi
David B Corry
Amber U Luong
John Morgan Knight

Publication Date

1-1-2022

Journal

Frontiers in Immunology

Abstract

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing the spliceosome, osteoclast differentiation, and coagulation pathways. Utilizing a specific inhibitor and gene-deficient mice, we demonstrate that STAT6 is required for mycosis-induced sinus inflammation. These findings confirm the relevance of this new model and portend future studies that further extend our understanding of the immunopathologic basis of airway mycosis and unified airway disease.

Keywords

STAT-6, allergic, mycosis, asthma, chronic rhinosinusitis, mouse model, unified airway, eosinophil

Comments

Supplementary Materials

PMID: 35281012