Imperial College London
Alternate

ProfessorStuartCook

Faculty of Medicine, Institute of Clinical Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 1346stuart.cook

 
 
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Location

 

RF 16Sydney StreetRoyal Brompton 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}
}
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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  -
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