Imperial College London

DrAdamByrne

Faculty of MedicineNational Heart & Lung Institute

Lecturer in Chronic Lung Disease
 
 
 
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Contact

 

a.byrne

 
 
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Location

 

369Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ng:2019:10.1126/scitranslmed.aaw1237,
author = {Ng, B and Dong, J and D'Agostino, G and Viswanathan, S and Widjaja, AA and Lim, W-W and Ko, NSJ and Tan, J and Chothani, SP and Huang, B and Xie, C and Pua, CJ and Chacko, A-M and Guimaraes-Camboa, N and Evans, SM and Byrne, AJ and Maher, TM and Liang, J and Jiang, D and Noble, PW and Schafer, S and Cook, SA},
doi = {10.1126/scitranslmed.aaw1237},
journal = {Science Translational Medicine},
pages = {1--14},
title = {Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis},
url = {http://dx.doi.org/10.1126/scitranslmed.aaw1237},
volume = {11},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease where invasive pulmonary myofibroblasts secrete collagen and destroy lung integrity. Here, we show that interleukin-11 (IL11) is up-regulated in the lung of patients with IPF, associated with disease severity, and IL-11 is secreted from IPF fibroblasts. In vitro, IL-11 stimulates lung fibroblasts to become invasive actin alpha 2, smooth muscle–positive (ACTA2+), collagen-secreting myofibroblasts in an extracellular signal–regulated kinase (ERK)–dependent, posttranscriptional manner. In mice, fibroblast-specific transgenic expression or administration of murine IL-11 induces lung myofibroblasts and causes lung fibrosis. IL-11 receptor subunit alpha-1 (Il11ra1)–deleted mice, whose lung fibroblasts are unresponsive to profibrotic stimulation, are protected from fibrosis in the bleomycin mouse model of pulmonary fibrosis. We generated an IL-11–neutralizing antibody that blocks lung fibroblast activation downstream of multiple stimuli and reverses myofibroblast activation. In therapeutic studies, anti–IL-11 treatment diminished lung inflammation and reversed lung fibrosis while inhibiting ERK and SMAD activation in mice. These data prioritize IL-11 as a drug target for lung fibrosis and IPF.
AU - Ng,B
AU - Dong,J
AU - D'Agostino,G
AU - Viswanathan,S
AU - Widjaja,AA
AU - Lim,W-W
AU - Ko,NSJ
AU - Tan,J
AU - Chothani,SP
AU - Huang,B
AU - Xie,C
AU - Pua,CJ
AU - Chacko,A-M
AU - Guimaraes-Camboa,N
AU - Evans,SM
AU - Byrne,AJ
AU - Maher,TM
AU - Liang,J
AU - Jiang,D
AU - Noble,PW
AU - Schafer,S
AU - Cook,SA
DO - 10.1126/scitranslmed.aaw1237
EP - 14
PY - 2019///
SN - 1946-6234
SP - 1
TI - Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis
T2 - Science Translational Medicine
UR - http://dx.doi.org/10.1126/scitranslmed.aaw1237
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000487828700003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://stm.sciencemag.org/content/11/511/eaaw1237/
VL - 11
ER -