Frontline Science: Shh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma
AffiliationUniversity of Bedfordshire
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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.
CitationStanding ASI, Yanez DC, Ross R, Crompton T, Furmanski AL (2017) 'Frontline Science: 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, 102 (4), pp.965-976.
PublisherSociety for Leukocyte Biology
JournalJournal of Leukocyte Biology
PubMed Central IDPMC5597515
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- Creative Commons
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