Imperial College London
Alternate

Professor Trevor Hansel

Faculty of Medicine, National Heart & Lung Institute

Emeritus Professor of Respiratory Pharmacology
 
 
 
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Contact

 

+44 (0)20 3312 5733t.hansel

 
 
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Location

 

Imperial Clinical Respiratory ReMint WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jha:2019:10.1183/23120541.lungscienceconference-2019.OP01,
author = {Jha, A and Thwaites, R and Tunstall, T and Kon, OM and Shattock, R and Openshaw, P and Hansel, T},
doi = {10.1183/23120541.lungscienceconference-2019.OP01},
journal = {ERJ Open Research},
title = {Enhanced in vivo vivo mucosal interferon and chemokine responses to a single stranded RNA analogue (R848) in participants with asthma},
url = {http://dx.doi.org/10.1183/23120541.lungscienceconference-2019.OP01},
volume = {5},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Viruses play an important role in asthma exacerbations and are detected by Toll-like receptors (TLRs). Better characterization of mucosal innate immunity to viral triggers may help understand dysregulated host responses in asthma.Aims & Objectives: A synthetic analogue of single-stranded RNA (ssRNA) and TLR7/8 agonist resiquimod (R848) was administered in vivo to study the effect of allergy and asthma on nasal mucosal innate immune responses.Methods: Nasal spray with saline and R848 was administered to healthy non-allergic (n=12), allergic rhinitis (n=12) and allergic asthma (n=11) participants. Immune mediators from nasal and blood samples, nasal mucosal gene expression and peripheral differential cell counts were measured.Results: R848 was well tolerated with no evidence of systemic immune activation. R848 significantly induced nasal mucosal IFN-a2a, IFN-?, pro-inflammatory cytokines (TNF-a, IL-2, IL-12p70) and chemokines (CXCL10, CCL2, CCL3, CCL4 and CCL13) compared to saline. Participants with allergic rhinitis and asthma had increased IFN-a2a, CCL3 and CCL13 relative to healthy participants, whilst those with asthma alone had increased gene expression of interferon stimulated genes DDX58, MX1 and IFIT3. Nasal R848 administration was associated with a decrease in blood eosinophils at 4h and decrease in peripheral lymphocytes at 24h, a finding restricted to participants with allergic rhinitis and asthma.Conclusions: These results confirm the suitability of nasal delivery of R848 as a non-invasive tool to assess mucosal innate immunity and highlights a key role for asthma in determining host responses to viral RNA analogues.
AU  - Jha,A
AU  - Thwaites,R
AU  - Tunstall,T
AU  - Kon,OM
AU  - Shattock,R
AU  - Openshaw,P
AU  - Hansel,T
DO  - 10.1183/23120541.lungscienceconference-2019.OP01
PY  - 2019///
SN  - 2312-0541
TI  - Enhanced in vivo vivo mucosal interferon and chemokine responses to a single stranded RNA analogue (R848) in participants with asthma
T2  - ERJ Open Research
UR  - http://dx.doi.org/10.1183/23120541.lungscienceconference-2019.OP01
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000535806500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://openres.ersjournals.com/content/5/suppl_2/OP01
UR  - http://hdl.handle.net/10044/1/79682
VL  - 5
ER  -
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