Abstract
Eosinophils are implicated as effector cells in asthma but the functional implications of the precise location of eosinophils in the airway wall is poorly understood. We aimed to quantify eosinophils in the different compartments of the airway wall and associate these findings with clinical features of asthma and markers of airway inflammation.
In this cross-sectional study, we utilised design-based stereology to accurately partition the numerical density of eosinophils in both the epithelial compartment and the subepithelial space (airway wall area below the basal lamina including the submucosa) in individuals with and without asthma and related these findings to airway hyperresponsiveness (AHR) and features of airway inflammation.
Intraepithelial eosinophils were linked to the presence of asthma and endogenous AHR, the type of AHR that is most specific for asthma. In contrast, both intraepithelial and subepithelial eosinophils were associated with type-2 (T2) inflammation, with the strongest association between IL5 expression and intraepithelial eosinophils. Eosinophil infiltration of the airway wall was linked to a specific mast cell phenotype that has been described in asthma. We found that IL-33 and IL-5 additively increased cysteinyl leukotriene (CysLT) production by eosinophils and that the CysLT LTC4 along with IL-33 increased IL13 expression in mast cells and altered their protease profile.
We conclude that intraepithelial eosinophils are associated with endogenous AHR and T2 inflammation and may interact with intraepithelial mast cells via CysLTs to regulate airway inflammation.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Al-Shaikhly reports In addition, Dr. Al-Shaikhly has a patent MicroRNAs as Predictors of Response to Anti-IgE Therapies in Chronic Spontaneous Urticaria pending.
Conflict of interest: Ryan C. Murphy has nothing to disclose.
Conflict of interest: Andrew Parker has nothing to disclose.
Conflict of interest: Ying Lai has nothing to disclose.
Conflict of interest: Matthew C. Altman reports personal fees from Sanofi-Regeneron, outside the submitted work.
Conflict of interest: Megan Larmore has nothing to disclose.
Conflict of interest: Dr. Altemeier reports grants from NIH, during the conduct of the study.
Conflict of interest: Charles W. Frevert has nothing to disclose.
Conflict of interest: Jason S. Debley reports grants from the National Institute of Health during the conduct of the study.
Conflict of interest: Dr. Piliponsky reports grants from National Institute of Health, outside the submitted work.
Conflict of interest: Steven F. Ziegler has nothing to disclose.
Conflict of interest: Dr. Peters reports grants from NIH-NHLBI, grants from Boeringer-Ingelheim, during the conduct of the study; grants from Astrazeneca, Boehringer-Ingelheim, Genentech,GlaxoSmithKline, Sanofi-Genzyme-Regeneron, and Teva, outside the submitted work.
Conflict of interest: Dr. Hallstrand reports grants from NIH, during the conduct of the study; grants from NIH, outside the submitted work.
- Received July 2, 2021.
- Accepted December 6, 2021.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
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