Respiratory syncytial virus induces functional thymic stromal lymphopoietin receptor in airway epithelial cells

Michael M Miazgowicz,1,2 Molly S Elliott,3 Jason S Debley,3 Steven F Ziegler1,21Immunology Program, Benaroya Research Institute, Seattle, WA, 2Department of Immunology, University of Washington School of Medicine, Seattle, WA, 3The Center for Immunology and Immunotherapies, Seattle Children'...

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Autores principales: Miazgowicz MM, Elliott MS, Debley JS, Ziegler SF
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Publicado: Dove Medical Press 2013
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spelling oai:doaj.org-article:6bf93b0d755147bf8062e2b944bf8b8b2021-12-02T03:17:14ZRespiratory syncytial virus induces functional thymic stromal lymphopoietin receptor in airway epithelial cells1178-7031https://doaj.org/article/6bf93b0d755147bf8062e2b944bf8b8b2013-03-01T00:00:00Zhttp://www.dovepress.com/respiratory-syncytial-virus-induces-functional-thymic-stromal-lymphopo-a12555https://doaj.org/toc/1178-7031Michael M Miazgowicz,1,2 Molly S Elliott,3 Jason S Debley,3 Steven F Ziegler1,21Immunology Program, Benaroya Research Institute, Seattle, WA, 2Department of Immunology, University of Washington School of Medicine, Seattle, WA, 3The Center for Immunology and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USAAbstract: The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) plays a key role in the development and progression of atopic disease and has notably been shown to directly promote the allergic inflammatory responses that characterize asthma. Current models suggest that TSLP is produced by epithelial cells in response to inflammatory stimuli and acts primarily upon dendritic cells to effect a T helper type 2-type inflammatory response. Recent reports, however, have shown that epithelial cells themselves are capable of expressing the TSLP receptor (TSLPR), and may thus directly contribute to a TSLP-dependent response. We report here that beyond simply expressing the receptor, epithelial cells are capable of dynamically regulating TSLPR in response to the same inflammatory cues that drive the production of TSLP, and that epithelial cells produce chemokine C–C motif ligand 17, a T helper type 2-associated chemokine, in response to stimulation with TSLP. These data suggest that a direct autocrine or paracrine response to TSLP by epithelial cells may initiate the initial waves of chemotaxis during an allergic inflammatory response. Intriguingly, we find that the regulation of TSLPR, unlike TSLP, is independent of nuclear factor kappa-light-chain-enhancer of activated B cells, suggesting that the cell may be able to independently regulate TSLP and TSLPR levels in order to properly modulate its response to TSLP. Finally, we show evidence for this dynamic regulation occurring following the viral infection of primary epithelial cells from asthmatic patients. Taken together, the data suggest that induction of TSLPR and a direct response to TSLP by epithelial cells may play a novel role in the development of allergic inflammation.Keywords: TSLP, TSLPR, RSV, asthma, epitheliumMiazgowicz MMElliott MSDebley JSZiegler SFDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2013, Iss default, Pp 53-61 (2013)
institution DOAJ
collection DOAJ
language EN
topic Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Miazgowicz MM
Elliott MS
Debley JS
Ziegler SF
Respiratory syncytial virus induces functional thymic stromal lymphopoietin receptor in airway epithelial cells
description Michael M Miazgowicz,1,2 Molly S Elliott,3 Jason S Debley,3 Steven F Ziegler1,21Immunology Program, Benaroya Research Institute, Seattle, WA, 2Department of Immunology, University of Washington School of Medicine, Seattle, WA, 3The Center for Immunology and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USAAbstract: The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) plays a key role in the development and progression of atopic disease and has notably been shown to directly promote the allergic inflammatory responses that characterize asthma. Current models suggest that TSLP is produced by epithelial cells in response to inflammatory stimuli and acts primarily upon dendritic cells to effect a T helper type 2-type inflammatory response. Recent reports, however, have shown that epithelial cells themselves are capable of expressing the TSLP receptor (TSLPR), and may thus directly contribute to a TSLP-dependent response. We report here that beyond simply expressing the receptor, epithelial cells are capable of dynamically regulating TSLPR in response to the same inflammatory cues that drive the production of TSLP, and that epithelial cells produce chemokine C–C motif ligand 17, a T helper type 2-associated chemokine, in response to stimulation with TSLP. These data suggest that a direct autocrine or paracrine response to TSLP by epithelial cells may initiate the initial waves of chemotaxis during an allergic inflammatory response. Intriguingly, we find that the regulation of TSLPR, unlike TSLP, is independent of nuclear factor kappa-light-chain-enhancer of activated B cells, suggesting that the cell may be able to independently regulate TSLP and TSLPR levels in order to properly modulate its response to TSLP. Finally, we show evidence for this dynamic regulation occurring following the viral infection of primary epithelial cells from asthmatic patients. Taken together, the data suggest that induction of TSLPR and a direct response to TSLP by epithelial cells may play a novel role in the development of allergic inflammation.Keywords: TSLP, TSLPR, RSV, asthma, epithelium
format article
author Miazgowicz MM
Elliott MS
Debley JS
Ziegler SF
author_facet Miazgowicz MM
Elliott MS
Debley JS
Ziegler SF
author_sort Miazgowicz MM
title Respiratory syncytial virus induces functional thymic stromal lymphopoietin receptor in airway epithelial cells
title_short Respiratory syncytial virus induces functional thymic stromal lymphopoietin receptor in airway epithelial cells
title_full Respiratory syncytial virus induces functional thymic stromal lymphopoietin receptor in airway epithelial cells
title_fullStr Respiratory syncytial virus induces functional thymic stromal lymphopoietin receptor in airway epithelial cells
title_full_unstemmed Respiratory syncytial virus induces functional thymic stromal lymphopoietin receptor in airway epithelial cells
title_sort respiratory syncytial virus induces functional thymic stromal lymphopoietin receptor in airway epithelial cells
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/6bf93b0d755147bf8062e2b944bf8b8b
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AT elliottms respiratorysyncytialvirusinducesfunctionalthymicstromallymphopoietinreceptorinairwayepithelialcells
AT debleyjs respiratorysyncytialvirusinducesfunctionalthymicstromallymphopoietinreceptorinairwayepithelialcells
AT zieglersf respiratorysyncytialvirusinducesfunctionalthymicstromallymphopoietinreceptorinairwayepithelialcells
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