1. IL-33 amplifies airways inflammation in a murine surrogate of asthma putatively via activation of dendritic cells.
- Author
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Wang, Wenjun, An, Gao, Li, Yan, Wang, Jingjing, Lv, Zhe, Chen, Yan, Corrigan, Chris J., Wang, Wei, Huang, Kewu, and Ying, Sun
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DENDRITIC cells , *AIRWAY (Anatomy) , *ASTHMA , *RESPIRATORY obstructions , *LUNG diseases - Abstract
• Mice challenged with Der f and IL-33 evinced more airway inflammation than Der f alone. • IL-33 induced airways inflammation of mice exposed to sub-threshold dosages of Der f. • Dendritic cells activated by IL-33 are more functional. 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+ 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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