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

@inproceedings{Pillar:2022:10.1111/resp.14226,
author = {Pillar, A and Brown, A and Mayall, J and Weaver, J and Essilfie, A and Hoefel, G and Ali, M and Kim, R and Donovan, C and Gomez, H and Vanka, K and Tay, H and Kermani, N and Guo, Y and Mumby, S and Adcock, I and Anderson, G and Fraser, D and Johnstone, D and Milward, E and Hansbro, P and Wark, P and Reid, D and Foster, P and Horvat, J},
doi = {10.1111/resp.14226},
pages = {105--105},
publisher = {Wiley},
title = {Relationship between interleukin-13 and transferrin receptor-1 responses in asthma pathogenesis},
url = {http://dx.doi.org/10.1111/resp.14226},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - CPAPER
AB  - Introduction/Aim: Clinical and experimental evidence highlights an important role for altered iron metabolism in the pathogenesis and severity of asthma. Elevated iron in airway cells and tissues and increased gene expression of the iron uptake protein, transferrin receptor (TFR)1, correlates with increased Type-2 (T2) cytokine responses, worsened lung function and development of key disease features. Here, we examined the relationship between the T2 cytokine, interleukin (IL)-13 and TFR1 in the pathogenesis of key features of asthma.Methods: Anti-TFR1 (αTFR1) and -IL-13 (αIL-13) was administered intranasally during a murine model of house dust mite (HDM)-induced asthma. The effects of αTFR1 or αIL-13 on inflammatory and TFR1+ cell numbers, collagen deposition and mucus secreting cell (MSC) numbers in the airways, iron metabolism, T2 and pro-inflammatory gene expression or lung function was assessed. The effects of IL-13 on TFR1 and matrix metalloprotease (MMP)9 responses in murine bone marrow derived macrophages (BMDM) was also assessed.Results: TFR1 is increased on macrophages and epithelial cells in HDM-induced asthma. αTFR1 reduces TFR1+ macrophages, but not TFR1+ epithelial cells, in disease. Importantly, αTFR1 reduces inflammation, fibrosis, MSC numbers, airflow obstruction in disease. αTFR1 has no effect on HDM-induced IL-13, but significantly suppresses MMP9, which is implicated in airway remodelling, expression in the lungs. IL-13 increases TFR1 expression in BMDMs and intranasal administration of αIL-13 reduces the numbers of TFR1+ macrophages in HDM-induced asthma. Significantly, the combination of IL-13 and HDM increases MMP9 expression in BMDMs.Conclusion: We show a critical role for IL-13-mediated increases in TFR1 responses in macrophages in driving the pathogenesis of asthma. These findings highlight the potential for the therapeutic manipulation of TFR1 and/or iron metabolism for the treatment of not o
AU  - Pillar,A
AU  - Brown,A
AU  - Mayall,J
AU  - Weaver,J
AU  - Essilfie,A
AU  - Hoefel,G
AU  - Ali,M
AU  - Kim,R
AU  - Donovan,C
AU  - Gomez,H
AU  - Vanka,K
AU  - Tay,H
AU  - Kermani,N
AU  - Guo,Y
AU  - Mumby,S
AU  - Adcock,I
AU  - Anderson,G
AU  - Fraser,D
AU  - Johnstone,D
AU  - Milward,E
AU  - Hansbro,P
AU  - Wark,P
AU  - Reid,D
AU  - Foster,P
AU  - Horvat,J
DO  - 10.1111/resp.14226
EP  - 105
PB  - Wiley
PY  - 2022///
SN  - 1323-7799
SP  - 105
TI  - Relationship between interleukin-13 and transferrin receptor-1 responses in asthma pathogenesis
UR  - http://dx.doi.org/10.1111/resp.14226
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000769654800168&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://onlinelibrary.wiley.com/doi/full/10.1111/resp.14226
UR  - http://hdl.handle.net/10044/1/97283
ER  -
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