Imperial College London
Alternate

ProfessorClareLloyd

Faculty of Medicine, National Heart & Lung Institute

Interim Head of NHLI, Vice-Dean (institutional Affairs) FoM
 
 
 
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Contact

 

+44 (0)20 7594 3102c.lloyd Website

 
 
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Location

 

Office 352Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{McErlean:2021:10.1164/rccm.202101-0004OC,
author = {McErlean, P and Bell, CG and Hewitt, RJ and Busharat, Z and Ogger, PP and Ghai, P and Albers, GJ and Calamita, E and Kingston, S and Molyneaux, PL and Beck, S and Lloyd, CM and Maher, TM and Byrne, AJ},
doi = {10.1164/rccm.202101-0004OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {954--966},
title = {DNA methylome alterations are associated with airway macrophage differentiation and phenotype during lung fibrosis.},
url = {http://dx.doi.org/10.1164/rccm.202101-0004OC},
volume = {204},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Rationale: Airway macrophages (AMs) are key regulators of the lung environment and are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a fatal respiratory disease with no cure. However, knowledge about the epigenetics of AMs in IPF is limited. Objectives: To assess the role of epigenetic regulation of AMs during lung fibrosis. Methods: We undertook DNA methylation (DNAm) profiling by using Illumina EPIC (850k) arrays in sorted AMs from healthy donors (n = 14) and donors with IPF (n = 30). Cell-type deconvolution was performed by using reference myeloid-cell DNA methylomes. Measurements and Main Results: Our analysis revealed that epigenetic heterogeneity was a key characteristic of IPF AMs. DNAm "clock" analysis indicated that epigenetic alterations in IPF AMs were not associated with accelerated aging. In differential DNAm analysis, we identified numerous differentially methylated positions (n = 11) and differentially methylated regions (n = 49) between healthy and IPF AMs, respectively. Differentially methylated positions and differentially methylated regions encompassed genes involved in lipid (LPCAT1 [lysophosphatidylcholine acyltransferase 1]) and glucose (PFKFB3 [6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3]) metabolism, and importantly, the DNAm status was associated with disease severity in IPF. Conclusions: Collectively, our data identify that changes in the epigenome are associated with the development and function of AMs in the IPF lung.
AU  - McErlean,P
AU  - Bell,CG
AU  - Hewitt,RJ
AU  - Busharat,Z
AU  - Ogger,PP
AU  - Ghai,P
AU  - Albers,GJ
AU  - Calamita,E
AU  - Kingston,S
AU  - Molyneaux,PL
AU  - Beck,S
AU  - Lloyd,CM
AU  - Maher,TM
AU  - Byrne,AJ
DO  - 10.1164/rccm.202101-0004OC
EP  - 966
PY  - 2021///
SN  - 1073-449X
SP  - 954
TI  - DNA methylome alterations are associated with airway macrophage differentiation and phenotype during lung fibrosis.
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.202101-0004OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34280322
UR  - https://www.atsjournals.org/doi/10.1164/rccm.202101-0004OC
UR  - http://hdl.handle.net/10044/1/92349
VL  - 204
ER  -
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