- Title
- Relationship between type 2 cytokine and inflammasome responses in obesity-associated asthma
- Creator
- Pinkerton, James W.; Kim, Richard Y.; Baines, Katherine J.; Starkey, Malcolm R.; Kermani, Nazanin Z.; Guo, Yi-Ke; Robertson, Avril A. B.; O'Neill, Luke A. J.; Adcock, Ian M.; Cooper, Matthew A.; Gibson, Peter G.; Wood, Lisa G.; Brown, Alexandra C.; Hansbro, Philip M.; Horvat, Jay C.; Rae, Brittany E.; Donovan, Chantal; Mayall, Jemma R.; Carroll, Olivia R.; Ali, Md. Khadem; Scott, Hayley A.; Berthon, Bronwyn S.
- Relation
- NHMRC.1120252 http://purl.org/au-research/grants/nhmrc/1120252
- Relation
- Journal of Allergy and Clinical Immunology Vol. 149, Issue 4, p. 1270-1280
- Publisher Link
- http://dx.doi.org/10.1016/j.jaci.2021.10.003
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2022
- Description
- Background: Obesity is a risk factor for asthma, and obese asthmatic individuals are more likely to have severe, steroid-insensitive disease. How obesity affects the pathogenesis and severity of asthma is poorly understood. Roles for increased inflammasome-mediated neutrophilic responses, type 2 immunity, and eosinophilic inflammation have been described. Objective: We investigated how obesity affects the pathogenesis and severity of asthma and identified effective therapies for obesity-associated disease. Methods: We assessed associations between body mass index and inflammasome responses with type 2 (T2) immune responses in the sputum of 25 subjects with asthma. Functional roles for NLR family, pyrin domain–containing (NLRP) 3 inflammasome and T2 cytokine responses in driving key features of disease were examined in experimental high-fat diet–induced obesity and asthma. Results: Body mass index and inflammasome responses positively correlated with increased IL-5 and IL-13 expression as well as C-C chemokine receptor type 3 expression in the sputum of subjects with asthma. High-fat diet–induced obesity resulted in steroid-insensitive airway hyperresponsiveness in both the presence and absence of experimental asthma. High-fat diet–induced obesity was also associated with increased NLRP3 inflammasome responses and eosinophilic inflammation in airway tissue, but not lumen, in experimental asthma. Inhibition of NLRP3 inflammasome responses reduced steroid-insensitive airway hyperresponsiveness but had no effect on IL-5 or IL-13 responses in experimental asthma. Depletion of IL-5 and IL-13 reduced obesity-induced NLRP3 inflammasome responses and steroid-insensitive airway hyperresponsiveness in experimental asthma. Conclusion: We found a relationship between T2 cytokine and NLRP3 inflammasome responses in obesity-associated asthma, highlighting the potential utility of T2 cytokine–targeted biologics and inflammasome inhibitors.
- Subject
- asthma; obesity; IL-5; IL-13; NLRP3 inflammasomes; SDG 3; SDG 10; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1464639
- Identifier
- uon:47060
- Identifier
- ISSN:0091-6749
- Language
- eng
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