Imperial College London
Alternate

ProfessorFanChung

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7954f.chung Website

 
 
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Assistant

 

Miss Carolyn Green +44 (0)20 7594 7959

 
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Location

 

227BGuy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tiotiu:2021:10.1111/all.14535,
author = {Tiotiu, A and Zounemat, Kermani N and Badi, Y and Pavlidis, S and Hansbro, PM and Guo, Y-K and Chung, KF and Adcock, IM and U-BIOPRED, consortium project team},
doi = {10.1111/all.14535},
journal = {Allergy},
pages = {775--788},
title = {Sputum macrophage diversity and activation in asthma: role of severity and inflammatory phenotype},
url = {http://dx.doi.org/10.1111/all.14535},
volume = {76},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Macrophages control innate and acquired immunity but their role in severe asthma remains ill-defined. We investigated gene signatures of macrophage subtypes in the sputum of 104 asthmatics and 16 healthy volunteers from the U-BIOPRED cohort. METHODS: Forty-nine gene signatures (modules) for differentially stimulated macrophages, one to assess lung tissue-resident cells (TR-Mφ) and two for their polarization (classically- and alternatively-activated macrophages: M1 and M2 respectively) were studied using gene set variation analysis. We calculated enrichment scores (ES) across severity and previously identified asthma transcriptome-associated clusters (TACs). RESULTS: Macrophage numbers were significantly decreased in severe asthma compared to mild-moderate asthma and healthy volunteers. The ES for most modules were also significantly reduced in severe asthma except for 3 associated with inflammatory responses driven by TNF and Toll-like receptors via NF-κB, eicosanoid biosynthesis via the lipoxygenase pathway and IL-2 biosynthesis (all p<0.01). Sputum macrophage number and the ES for most macrophage signatures were higher in the TAC3 group compared to TAC1 and TAC2 asthmatics. However, a high enrichment was found in TAC1 for 3 modules showing inflammatory pathways linked to Toll-like and TNF receptor activation and arachidonic acid metabolism (p<0.001) and in TAC2 for the inflammasome- and interferon-signalling pathways (p<0.001). Data was validated in the ADEPT cohort. Module analysis provides additional information compared to conventional M1 and M2 classification. TR-Mφ were enriched in TAC3 and associated with mitochondrial function. CONCLUSIONS: Macrophage activation is attenuated in severe granulocytic asthma highlighting defective innate immunity except for specific subsets characterised by distinct inflammatory pathways.
AU  - Tiotiu,A
AU  - Zounemat,Kermani N
AU  - Badi,Y
AU  - Pavlidis,S
AU  - Hansbro,PM
AU  - Guo,Y-K
AU  - Chung,KF
AU  - Adcock,IM
AU  - U-BIOPRED,consortium project team
DO  - 10.1111/all.14535
EP  - 788
PY  - 2021///
SN  - 0105-4538
SP  - 775
TI  - Sputum macrophage diversity and activation in asthma: role of severity and inflammatory phenotype
T2  - Allergy
UR  - http://dx.doi.org/10.1111/all.14535
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32740964
UR  - https://onlinelibrary.wiley.com/doi/full/10.1111/all.14535
UR  - http://hdl.handle.net/10044/1/81742
VL  - 76
ER  -
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