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Bronchial Allergen Challenge of Patients with Atopic Asthma Triggers an Alarmin (IL-33, TSLP, and IL-25) Response in the Airways Epithelium and Submucosa.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Oct 15; Vol. 201 (8), pp. 2221-2231. Date of Electronic Publication: 2018 Sep 05. - Publication Year :
- 2018
-
Abstract
- The alarmin cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) play a critical role in asthma pathogenesis by inducing mucosal Th2-type cytokine production. Although environmental exposure to aeroallergens has been proposed as an alarmin trigger in asthma, there has been no systematic parallel study of the effects of allergen exposure on the expression of these cytokines in the airways of human asthmatics. Using single and sequential double immunohistochemistry, we evaluated the numbers and phenotypes of IL-25-, IL-33-, and TSLP-immunoreactive cells in sections of bronchial biopsies from mild atopic asthmatics ( n = 16) before and 24 h after allergen inhalational challenge. Allergen challenge highly increased expression of baseline immunoreactivity for IL-25, IL-33, and TSLP, both in the bronchial epithelium and submucosa ( p < 0.001), to a degree that correlated with the extent of the late phase of airway obstruction. Aside from epithelial cells, the principal source of immunoreactivity for all three alarmins, TSLP, and IL-33 immunoreactivity colocalized principally with endothelial cells and mast cells, neutrophils, and fibroblasts, whereas IL-25 immunoreactivity colocalized principally with eosinophils as well as endothelial cells, mast cells, and fibroblasts. The data implicate that allergen challenge directly increases airway alarmin expression in atopic asthmatics to a degree correlating with increase late-phase airway obstruction, affirming these molecules as potential molecular targets for the inhibition of allergen-induced airway inflammation and obstruction.<br /> (Copyright © 2018 by The American Association of Immunologists, Inc.)
- Subjects :
- Administration, Inhalation
Adult
Airway Obstruction
Allergens immunology
Asthma diagnosis
Bronchial Provocation Tests
Cytokines metabolism
Female
Humans
Hypersensitivity, Immediate diagnosis
Immunohistochemistry
Interleukin-17 metabolism
Interleukin-33 metabolism
Male
Middle Aged
Respiratory Mucosa pathology
Young Adult
Thymic Stromal Lymphopoietin
Alarmins metabolism
Asthma immunology
Eosinophils immunology
Hypersensitivity, Immediate immunology
Neutrophils immunology
Respiratory Mucosa immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 201
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 30185520
- Full Text :
- https://doi.org/10.4049/jimmunol.1800709