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@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}
}
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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