Imperial College London
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ProfessorIanAdcock

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Cell & Molecular Biology
 
 
 
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Contact

 

+44 (0)20 7594 7840ian.adcock Website

 
 
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Location

 

304Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pinkerton:2022:10.1016/j.jaci.2021.10.003,
author = {Pinkerton, JW and Kim, RY and Brown, AC and Rae, BE and Donovan, C and Mayall, JR and Carroll, OR and Khadem, Ali M and Scott, HA and Berthon, BS and Baines, KJ and Starkey, MR and Kermani, NZ and Guo, Y-K and Robertson, AAB and O'Neill, LAJ and Adcock, IM and Cooper, MA and Gibson, PG and Wood, LG and Hansbro, PM and Horvat, JC},
doi = {10.1016/j.jaci.2021.10.003},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1270--1280},
title = {Relationship between type 2 cytokine and inflammasome responses in obesity-associated asthma},
url = {http://dx.doi.org/10.1016/j.jaci.2021.10.003},
volume = {149},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Pinkerton,JW
AU  - Kim,RY
AU  - Brown,AC
AU  - Rae,BE
AU  - Donovan,C
AU  - Mayall,JR
AU  - Carroll,OR
AU  - Khadem,Ali M
AU  - Scott,HA
AU  - Berthon,BS
AU  - Baines,KJ
AU  - Starkey,MR
AU  - Kermani,NZ
AU  - Guo,Y-K
AU  - Robertson,AAB
AU  - O'Neill,LAJ
AU  - Adcock,IM
AU  - Cooper,MA
AU  - Gibson,PG
AU  - Wood,LG
AU  - Hansbro,PM
AU  - Horvat,JC
DO  - 10.1016/j.jaci.2021.10.003
EP  - 1280
PY  - 2022///
SN  - 0091-6749
SP  - 1270
TI  - Relationship between type 2 cytokine and inflammasome responses in obesity-associated asthma
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2021.10.003
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34678326
UR  - https://www.sciencedirect.com/science/article/pii/S0091674921015256?via%3Dihub
UR  - http://hdl.handle.net/10044/1/92599
VL  - 149
ER  -
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