Relationship between type 2 cytokine and inflammasome responses in obesity-associated asthma
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Accepted version
Supplementary information
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2022-04-01
Date Acceptance
2021-10-01
ISSN
0091-6749
Publisher
Elsevier
Start Page
1270
End Page
1280
Journal / Book Title
Journal of Allergy and Clinical Immunology
Volume
149
Issue
4
Copyright Statement
© 2021 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Commission of the European Communities
Engineering & Physical Science Research Council (EPSRC)
Identifier
https://www.sciencedirect.com/science/article/pii/S0091674921015256?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/34678326
S0091-6749(21)01525-6
Grant Number
115010
EP/T003189/1
Subjects
Asthma
IL-13
IL-5
NLRP3 inflammasomes
obesity
Asthma
Cytokines
Humans
Inflammasomes
Inflammation
Interleukin-13
Interleukin-1beta
Interleukin-5
NLR Family, Pyrin Domain-Containing 3 Protein
Obesity
Humans
Asthma
Obesity
Inflammation
Interleukin-5
Interleukin-13
Cytokines
Interleukin-1beta
Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
Asthma
IL-13
IL-5
NLRP3 inflammasomes
obesity
Allergy
1107 Immunology
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-10-19