Imperial College London
Alternate

DrJonathanBaker

Faculty of Medicine, National Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 7790jonathan.baker

 
 
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Location

 

223Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Baker:2022:10.1172/jci.insight.155581,
author = {Baker, JR and Fenwick, PS and Koss, CK and Owles, HB and Elkin, SL and Fine, JS and Thomas, M and Kasmi, KC and Barnes, PJ and Donnelly, LE},
doi = {10.1172/jci.insight.155581},
journal = {JCI Insight},
title = {Imbalance between IL-36 receptor agonist and antagonist drives neutrophilic inflammation in COPD},
url = {http://dx.doi.org/10.1172/jci.insight.155581},
volume = {7},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Current treatments fail to modify the underlying pathophysiology and disease progression of chronic obstructive pulmonary disease (COPD), necessitating alternative therapies. Here, we show that COPD subjects have increased IL-36γ and decreased IL-36 receptor antagonist (IL-36Ra) in bronchoalveolar and nasal fluid compared to control subjects. IL-36γ is derived from small airway epithelial cells (SAEC) and further induced by a viral mimetic, whereas IL-36RA is derived from macrophages. IL-36γ stimulates release of the neutrophil chemoattractants CXCL1 and CXCL8, as well as elastolytic matrix metalloproteinases (MMPs) from small airway fibroblasts (SAF). Proteases released from COPD neutrophils cleave and activate IL-36γ thereby perpetuating IL-36 inflammation. Transfer of culture media from SAEC to SAF stimulated release of CXCL1, that was inhibited by exogenous IL-36RA. The use of a therapeutic antibody that inhibits binding to the IL-36 receptor (IL-36R) attenuated IL-36γ driven inflammation and cellular cross talk. We have demonstrated a mechanism for the amplification and propagation of neutrophilic inflammation in COPD and that blocking this cytokine family via a IL-36R neutralizing antibody could be a promising new therapeutic strategy in the treatment of COPD.
AU  - Baker,JR
AU  - Fenwick,PS
AU  - Koss,CK
AU  - Owles,HB
AU  - Elkin,SL
AU  - Fine,JS
AU  - Thomas,M
AU  - Kasmi,KC
AU  - Barnes,PJ
AU  - Donnelly,LE
DO  - 10.1172/jci.insight.155581
PY  - 2022///
SN  - 2379-3708
TI  - Imbalance between IL-36 receptor agonist and antagonist drives neutrophilic inflammation in COPD
T2  - JCI Insight
UR  - http://dx.doi.org/10.1172/jci.insight.155581
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35763349
UR  - https://insight.jci.org/articles/view/155581
UR  - http://hdl.handle.net/10044/1/97997
VL  - 7
ER  -
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