BibTex format
@article{Williams:2020:10.1165/rcmb.2020-0011OC,
author = {Williams, TC and Jackson, DJ and Maltby, S and Walton, RP and Ching, Y-M and Glanville, N and Singanayagam, A and Brewins, JJ and Clarke, D and Hirsman, AG and Loo, S-L and Wei, L and Beale, JE and Casolari, P and Caramori, G and Papi, A and Belvisi, M and Wark, PAB and Johnston, SL and Edwards, MR and Bartlett, NW},
doi = {10.1165/rcmb.2020-0011OC},
journal = {American Journal of Respiratory Cell and Molecular Biology},
pages = {344--356},
title = {Rhinovirus-induced CCL17 and CCL22 in asthma exacerbations and differential regulation by STAT6.},
url = {http://dx.doi.org/10.1165/rcmb.2020-0011OC},
volume = {64},
year = {2020}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The interplay of type-2 inflammation and anti-viral immunity underpins asthma exacerbation pathogenesis. Virus infection induces type-2 inflammation-promoting chemokines CCL17 and CCL22 in asthma, however mechanisms regulating induction are poorly understood. By using a human rhinovirus (RV) challenge model in human airway epithelial cells in vitro and mice in vivo, we assessed mechanisms regulating CCL17 and CCL22 expression. Subjects with mild-to-moderate asthma and healthy volunteers were experimentally infected with RV and airway CCL17 and CCL22 protein quantified. In vitro airway epithelial cell- and mouse-RV infection models were then employed to define STAT6- and NF-κB-mediated regulation of CCL17 and CCL22 expression. Following RV infection, CCL17 and CCL22 expression was higher in asthma, which differentially correlated with clinical and immunological parameters. Air-liquid interface (ALI) differentiated primary epithelial cells from donors with asthma also expressed higher levels of RV-induced CCL22. RV infection boosted type-2 cytokine-induced STAT6 activation. In epithelial cells, type-2 cytokines and STAT6 activation had differential effects on chemokine expression: increasing CCL17 and suppressing CCL22, whereas NF-κB promoted expression of both chemokines. In mice, RV infection activated pulmonary STAT6 which was required for CCL17, but not CCL22 expression. STAT6-knockout mice infected with RV expressed increased levels of NF-kB-regulated chemokines, which was associated with rapid viral clearance. Therefore, RV-induced upregulation of CCL17 and CCL22 was mediated by NF-κB activation, whereas expression was differentially regulated by STAT6. Together, findings suggest therapeutic targeting of type-2-STAT6 activation alone will not block all inflammatory pathways during RV infection in asthma.
AU - Williams,TC
AU - Jackson,DJ
AU - Maltby,S
AU - Walton,RP
AU - Ching,Y-M
AU - Glanville,N
AU - Singanayagam,A
AU - Brewins,JJ
AU - Clarke,D
AU - Hirsman,AG
AU - Loo,S-L
AU - Wei,L
AU - Beale,JE
AU - Casolari,P
AU - Caramori,G
AU - Papi,A
AU - Belvisi,M
AU - Wark,PAB
AU - Johnston,SL
AU - Edwards,MR
AU - Bartlett,NW
DO - 10.1165/rcmb.2020-0011OC
EP - 356
PY - 2020///
SN - 1044-1549
SP - 344
TI - Rhinovirus-induced CCL17 and CCL22 in asthma exacerbations and differential regulation by STAT6.
T2 - American Journal of Respiratory Cell and Molecular Biology
UR - http://dx.doi.org/10.1165/rcmb.2020-0011OC
UR - https://www.ncbi.nlm.nih.gov/pubmed/33264064
UR - https://www.atsjournals.org/doi/10.1165/rcmb.2020-0011OC
UR - http://hdl.handle.net/10044/1/85367
VL - 64
ER -
