Journal article
Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons
V Gielen, A Sykes, J Zhu, B Chan, J Macintyre, N Regamey, E Kieninger, A Gupta, A Shoemark, C Bossley, J Davies, S Saglani, P Walker, SE Nicholson, AH Dalpke, OM Kon, A Bush, SL Johnston, MR Edwards
Journal of Allergy and Clinical Immunology | Published : 2015
Abstract
Background Rhinovirus infections are the dominant cause of asthma exacerbations, and deficient virus induction of IFN-α/β/λ in asthmatic patients is important in asthma exacerbation pathogenesis. Mechanisms causing this interferon deficiency in asthmatic patients are unknown. Objective We sought to investigate the expression of suppressor of cytokine signaling (SOCS) 1 in tissues from asthmatic patients and its possible role in impaired virus-induced interferon induction in these patients. Methods We assessed SOCS1 mRNA and protein levels in vitro, bronchial biopsy specimens, and mice. The role of SOCS1 was inferred by proof-of-concept studies using overexpression with reporter genes and SOC..
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Funding Acknowledgements
V.G. was funded by a studentship from the National Heart Lung Institute Foundation, Imperial College London. M.R.E. was supported by a Fellowship and S.L.J. was supported by a Chair from Asthma UK (RF07_04, CH11SJ respectively). A.S. was funded by a MRC Clinical Research Fellowship. This work was supported in part by grants from the British Lung Foundation (P06/13), MRC project grant G0601236, MRC Centre grant G1000758, ERC FP7 Advanced grant 233015 (to SLJ), the National Institute of Health Research Biomedical Research Centre funding scheme, National Institute of Health Research BRC Project grant P26095, Predicta FP7 Collaborative Project grant 260895, and the Wellcome Trust-sponsored Centre for Respiratory Infection (CRI). A.B. was supported by the National Institute of Health Research Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. P.W. was supported by the German Research Foundation grants Da592/4 and SFB938. S.E.N. was supported by National Health and Medical Research Council Program grants 461219 and 1016647.