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IL-33 amplifies airways inflammation in a murine surrogate of asthma putatively via activation of dendritic cells.
- Source :
-
Cellular immunology [Cell Immunol] 2021 Aug; Vol. 366, pp. 104395. Date of Electronic Publication: 2021 Jun 15. - Publication Year :
- 2021
-
Abstract
- Although contributions of IL-33 to pulmonary diseases, including asthma, have been well documented, the complexity of such regulation warrants additional exploration. To better understand the involvement of IL-33, we used a murine asthma surrogate based on sensitisation and challenge with dust mite extract in the presence/absence of IL-33. Murine models were established with Dermatophagoides farinae (Der f) to establish (1) the effect of co-administered rmIL-33; (2) the effect of prior glucocorticoid intervention; (3) the effect of IL-33 on challenge with sub-threshold dosage Der f. The effects of rmIL-33 on bone marrow-derived dendritic cells were explored in vitro. Mice challenged with Der f combined with IL-33 compared with diluent control evinced significantly more airways inflammation and local cytokine production which was less sensitive to inhibition by dexamethasone. IL-33 also induced airways hyperresponsiveness, eosinophilic inflammation and cytokine production in lung tissues of animals exposed to sub-threshold dosage of Der f. In vitro, IL-33-stimulated DCs showed a significantly elevated capacity to stimulate CD4 <superscript>+</superscript> T cell proliferation and cytokine production and were also significantly more resistant to dexamethasone-induced apoptosis. Our data suggest that IL-33 reduces the threshold for allergen-induced inflammation of the airways in acorticosteroid-resistant fashion possibly in part through acting on DCs, a phenomenon which may be relevant to the development of severe, corticosteroid-resistant airways obstruction in human asthmatic patients.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Anti-Allergic Agents therapeutic use
Antigens, Dermatophagoides immunology
Asthma drug therapy
Cell Differentiation
Cells, Cultured
Dermatophagoides farinae
Dexamethasone therapeutic use
Disease Models, Animal
Drug Resistance
Female
Humans
Inflammation drug therapy
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Asthma immunology
CD4-Positive T-Lymphocytes immunology
Dendritic Cells immunology
Inflammation immunology
Interleukin-33 metabolism
Respiratory System immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2163
- Volume :
- 366
- Database :
- MEDLINE
- Journal :
- Cellular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34198027
- Full Text :
- https://doi.org/10.1016/j.cellimm.2021.104395