Shh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma

2.50
Hdl Handle:
http://hdl.handle.net/10547/622069
Title:
Shh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma
Authors:
Standing, Ariane S.I.; Yánez, Diane C.; Ross, Rosie; Crompton, Tessa ( 0000-0002-8973-4021 ) ; Furmanski, Anna L.
Abstract:
The pathophysiology of allergic asthma is driven by T-helper 2 (Th2) immune responses following aeroallergen inhalation. The mechanisms that initiate, potentiate and regulate airways allergy are incompletely characterized. We have previously shown that Hedgehog (Hh) signaling to T-cells, via downstream Gli transcription factors, enhances T-cell conversion to a Th2 phenotype. Here, we show for the first time that Gli-dependent transcription is activated in T-cells in vivo during murine allergic airways disease (AAD) a model for the immunopathology of asthma; and that genetic repression of Gli signaling in Tcells decreases the differentiation and/or recruitment of Th2 cells to the lung. We report that T-cells are not the only cells capable of expressing activated Gli during AAD. A substantial proportion of eosinophils and lung epithelial cells, both central mediators of the immunopathology of asthma, are also able to undergo Hh/Gli signaling. Finally, we show that Shh increases Il4 expression in eosinophils. We therefore propose that Hh signaling during AAD is complex, involving multiple cell types, signaling in an auto- or paracrine fashion. Improved understanding of the role of this major morphogenetic pathway in asthma may give rise to new drug targets for this chronic condition.
Affiliation:
University of Bedfordshire
Citation:
Standing ASI, Yanez DC, Ross R, Crompton T, Furmanski AL (2017) 'Shh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma', Journal of Leukocyte Biology.
Publisher:
Society for Leukocyte Biology
Journal:
Journal of Leukocyte Biology
Issue Date:
24-Feb-2017
URI:
http://hdl.handle.net/10547/622069
DOI:
10.1189/jlb.3HI1016-438RR
PubMed ID:
28235772
Additional Links:
http://www.jleukbio.org/content/early/2017/02/24/jlb.3HI1016-438RR.abstract
Type:
Article
Language:
en
ISSN:
0741-5400
Appears in Collections:
Biomedical and biological science

Full metadata record

DC FieldValue Language
dc.contributor.authorStanding, Ariane S.I.en
dc.contributor.authorYánez, Diane C.en
dc.contributor.authorRoss, Rosieen
dc.contributor.authorCrompton, Tessaen
dc.contributor.authorFurmanski, Anna L.en
dc.date.accessioned2017-03-24T11:26:42Z-
dc.date.available2017-03-24T11:26:42Z-
dc.date.issued2017-02-24-
dc.identifier.citationStanding ASI, Yanez DC, Ross R, Crompton T, Furmanski AL (2017) 'Shh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma', Journal of Leukocyte Biology.en
dc.identifier.issn0741-5400-
dc.identifier.pmid28235772-
dc.identifier.doi10.1189/jlb.3HI1016-438RR-
dc.identifier.urihttp://hdl.handle.net/10547/622069-
dc.description.abstractThe pathophysiology of allergic asthma is driven by T-helper 2 (Th2) immune responses following aeroallergen inhalation. The mechanisms that initiate, potentiate and regulate airways allergy are incompletely characterized. We have previously shown that Hedgehog (Hh) signaling to T-cells, via downstream Gli transcription factors, enhances T-cell conversion to a Th2 phenotype. Here, we show for the first time that Gli-dependent transcription is activated in T-cells in vivo during murine allergic airways disease (AAD) a model for the immunopathology of asthma; and that genetic repression of Gli signaling in Tcells decreases the differentiation and/or recruitment of Th2 cells to the lung. We report that T-cells are not the only cells capable of expressing activated Gli during AAD. A substantial proportion of eosinophils and lung epithelial cells, both central mediators of the immunopathology of asthma, are also able to undergo Hh/Gli signaling. Finally, we show that Shh increases Il4 expression in eosinophils. We therefore propose that Hh signaling during AAD is complex, involving multiple cell types, signaling in an auto- or paracrine fashion. Improved understanding of the role of this major morphogenetic pathway in asthma may give rise to new drug targets for this chronic condition.en
dc.language.isoenen
dc.publisherSociety for Leukocyte Biologyen
dc.relation.urlhttp://www.jleukbio.org/content/early/2017/02/24/jlb.3HI1016-438RR.abstracten
dc.rightsWhite - archiving not formally supported-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectimmunologyen
dc.subjectGli1en
dc.subjectSonic Hedgehogen
dc.subjectallergyen
dc.subjectepitheliaen
dc.subjectmorphogenen
dc.subjectepithelial cellsen
dc.subjectC550 Immunologyen
dc.titleShh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthmaen
dc.typeArticleen
dc.contributor.departmentUniversity of Bedfordshireen
dc.identifier.journalJournal of Leukocyte Biologyen
dc.date.updated2017-03-24T11:06:11Z-

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in UOBREP are protected by copyright, with all rights reserved, unless otherwise indicated.