Imperial College London
Alternate

ProfessorSebastianJohnston

Faculty of Medicine, National Heart & Lung Institute

Asthma UK Clinical Chair
 
 
 
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Contact

 

+44 (0)7931 376 544s.johnston

 
 
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Assistant

 

Mr Christophe Tytgat +44 (0)20 7594 3849

 
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Location

 

343Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Collison:2021:10.1172/jci.insight.127933,
author = {Collison, AM and Sokulsky, LA and Kepreotes, E and Pereira, de Siqueira A and Morten, M and Edwards, MR and Walton, RP and Bartlett, NW and Yang, M and Nguyen, TH and Johnston, SL and Foster, PS and Mattes, J},
doi = {10.1172/jci.insight.127933},
journal = {JCI Insight},
title = {miR-122 promotes virus-induced lung disease by targeting SOCS1},
url = {http://dx.doi.org/10.1172/jci.insight.127933},
volume = {6},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Virus-induced respiratory tract infections are a major health burden in childhood, and available treatments are supportive rather than disease modifying. Rhinoviruses (RVs), the cause of approximately 80% of common colds, are detected in nearly half of all infants with bronchiolitis and the majority of children with an asthma exacerbation. Bronchiolitis in early life is a strong risk factor for the development of asthma. Here, we found that RV infection induced the expression of miRNA 122 (miR-122) in mouse lungs and in human airway epithelial cells. In vivo inhibition specifically in the lung reduced neutrophilic inflammation and CXCL2 expression, boosted innate IFN responses, and ameliorated airway hyperreactivity in the absence and in the presence of allergic lung inflammation. Inhibition of miR-122 in the lung increased the levels of suppressor of cytokine signaling 1 (SOCS1), which is an in vitro-validated target of miR-122. Importantly, gene silencing of SOCS1 in vivo completely reversed the protective effects of miR-122 inhibition on RV-induced lung disease. Higher miR-122 expression in nasopharyngeal aspirates was associated with a longer time on oxygen therapy and a higher rate of treatment failure in 87 infants hospitalized with moderately severe bronchiolitis. These results suggest that miR-122 promotes RV-induced lung disease via suppression of its target SOCS1 in vivo. Higher miR-122 expression was associated with worse clinical outcomes, highlighting the potential use of anti-miR-122 oligonucleotides, successfully trialed for treatment of hepatitis C, as potential therapeutics for RV-induced bronchiolitis and asthma exacerbations.
AU  - Collison,AM
AU  - Sokulsky,LA
AU  - Kepreotes,E
AU  - Pereira,de Siqueira A
AU  - Morten,M
AU  - Edwards,MR
AU  - Walton,RP
AU  - Bartlett,NW
AU  - Yang,M
AU  - Nguyen,TH
AU  - Johnston,SL
AU  - Foster,PS
AU  - Mattes,J
DO  - 10.1172/jci.insight.127933
PY  - 2021///
SN  - 2379-3708
TI  - miR-122 promotes virus-induced lung disease by targeting SOCS1
T2  - JCI Insight
UR  - http://dx.doi.org/10.1172/jci.insight.127933
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33830082
UR  - http://hdl.handle.net/10044/1/92215
VL  - 6
ER  -
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