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Airway epithelium-shifted mast cell infiltration regulates asthmatic inflammation via IL-33 signaling
- Source :
- Journal of Clinical Investigation. November, 2019, Vol. 129 Issue 11, p4979, 13 p.
- Publication Year :
- 2019
-
Abstract
- Asthma is a heterogeneous syndrome that has been subdivided into physiologic phenotypes and molecular endotypes. The most specific phenotypic manifestation of asthma is indirect airway hyperresponsiveness (AHR), and a prominent molecular endotype is the presence of type 2 inflammation. The underlying basis for type 2 inflammation and its relationship to AHR are incompletely understood. We assessed the expression of type 2 cytokines in the airways of subjects with and without asthma who were extensively characterized for AHR. Using quantitative morphometry of the airway wall, we identified a shift in mast cells from the submucosa to the airway epithelium specifically associated with both type 2 inflammation and indirect AHR. Using ex vivo modeling of primary airway epithelial cells in organotypic coculture with mast cells, we show that epithelial-derived IL-33 uniquely induced type 2 cytokines in mast cells, which regulated the expression of epithelial IL33 in a feed-forward loop. This feed-forward loop was accentuated in epithelial cells derived from subjects with asthma. These results demonstrate that type 2 inflammation and indirect AHR in asthma are related to a shift in mast cell infiltration to the airway epithelium, and that mast cells cooperate with epithelial cells through IL-33 signaling to regulate type 2 inflammation.<br />Introduction Asthma is a heterogeneous disorder with features of airway inflammation, reversible airflow obstruction, and airway hyperresponsiveness (AHR). Indirect AHR is a particularly important pathophysiologic finding because it is a [...]
- Subjects :
- Cytokines
Inflammation
Asthma
Epithelium
Phenotypes
Health care industry
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 129
- Issue :
- 11
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.609854904
- Full Text :
- https://doi.org/10.1172/JCI126402