Imperial College London
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ProfessorPhilipMolyneaux

Faculty of Medicine, National Heart & Lung Institute

Professor of Interstitial Lung Disease
 
 
 
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Contact

 

p.molyneaux

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ogger:2020:10.1126/sciimmunol.abc1884,
author = {Ogger, PP and Albers, GJ and Hewitt, RJ and O'Sullivan, BJ and Powell, JE and Calamita, E and Ghai, P and Walker, SA and McErlean, P and Saunders, P and Kingston, S and Molyneaux, PL and Halket, JM and Gray, R and Chambers, DC and Maher, TM and Lloyd, CM and Byrne, AJ},
doi = {10.1126/sciimmunol.abc1884},
journal = {Science Immunology},
pages = {1--13},
title = {Itaconate controls the severity of pulmonary fibrosis},
url = {http://dx.doi.org/10.1126/sciimmunol.abc1884},
volume = {5},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease in which airway macrophages (AMs) play a key role. Itaconate has emerged as a mediator of macrophage function, but its role during fibrosis is unknown. Here, we reveal that itaconate is an endogenous antifibrotic factor in the lung. Itaconate levels are reduced in bronchoalveolar lavage, and itaconate-synthesizing cis-aconitate decarboxylase expression (ACOD1) is reduced in AMs from patients with IPF compared with controls. In the murine bleomycin model of pulmonary fibrosis, Acod1-/- mice develop persistent fibrosis, unlike wild-type (WT) littermates. Profibrotic gene expression is increased in Acod1-/- tissue-resident AMs compared with WT, and adoptive transfer of WT monocyte-recruited AMs rescued mice from disease phenotype. Culture of lung fibroblasts with itaconate decreased proliferation and wound healing capacity, and inhaled itaconate was protective in mice in vivo. Collectively, these data identify itaconate as critical for controlling the severity of lung fibrosis, and targeting this pathway may be a viable therapeutic strategy.
AU  - Ogger,PP
AU  - Albers,GJ
AU  - Hewitt,RJ
AU  - O'Sullivan,BJ
AU  - Powell,JE
AU  - Calamita,E
AU  - Ghai,P
AU  - Walker,SA
AU  - McErlean,P
AU  - Saunders,P
AU  - Kingston,S
AU  - Molyneaux,PL
AU  - Halket,JM
AU  - Gray,R
AU  - Chambers,DC
AU  - Maher,TM
AU  - Lloyd,CM
AU  - Byrne,AJ
DO  - 10.1126/sciimmunol.abc1884
EP  - 13
PY  - 2020///
SN  - 2470-9468
SP  - 1
TI  - Itaconate controls the severity of pulmonary fibrosis
T2  - Science Immunology
UR  - http://dx.doi.org/10.1126/sciimmunol.abc1884
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33097591
UR  - https://immunology.sciencemag.org/content/5/52/eabc1884/tab-article-info
UR  - http://hdl.handle.net/10044/1/84420
VL  - 5
ER  -
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