Imperial College London
Alternate

DR JAMES A HARKER

Faculty of Medicine, National Heart & Lung Institute

Senior Lecturer in Respiratory Science
 
 
 
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Contact

 

+44 (0)20 7594 3171j.harker

 
 
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Location

 

360Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pyle:2017:10.1371/journal.ppat.1006640,
author = {Pyle, CJ and Uwadiae, FI and Swieboda, DP and Harker, JA},
doi = {10.1371/journal.ppat.1006640},
journal = {PLoS Pathogens},
title = {Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology.},
url = {http://dx.doi.org/10.1371/journal.ppat.1006640},
volume = {13},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Interleukin-6 is a pleiotropic, pro-inflammatory cytokine that can promote both innate and adaptive immune responses. In humans with respiratory virus infections, such as Respiratory Syncytial Virus (RSV), elevated concentrations of IL-6 are associated with more severe disease. In contrast the polymorphisms in the Il6 promoter which favour lower IL-6 production are associated with increased risk of both RSV and Rhinovirus infections. To determine the precise contribution of IL-6 to protection and pathology we used murine models of respiratory virus infection. RSV infection resulted in increased IL-6 production both in the airways and systemically which remained heightened for at least 2 weeks. IL-6 depletion early, but not late, during RSV or Influenza A virus infection resulted in significantly increased disease associated with an influx of virus specific TH1 and cytotoxic CD8+ T cells, whilst not affecting viral clearance. IL-6 acted by driving production of the immunoregulatory cytokine IL-27 by macrophages and monocytes, which in turn promoted the local maturation of regulatory T cells. Concordantly IL-27 was necessary to regulate TH1 responses in the lungs, and sufficient to limit RSV induced disease. Overall we found that during respiratory virus infection the prototypic inflammatory cytokine IL-6 is a critical anti-inflammatory regulator of viral induced immunopathology in the respiratory tract through its induction of IL-27.
AU  - Pyle,CJ
AU  - Uwadiae,FI
AU  - Swieboda,DP
AU  - Harker,JA
DO  - 10.1371/journal.ppat.1006640
PY  - 2017///
SN  - 1553-7366
TI  - Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology.
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1006640
UR  - http://hdl.handle.net/10044/1/51340
VL  - 13
ER  -
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