Thymic stromal lymphopoietin plays divergent roles in murine models of atopic and nonatopic airway inflammation.

Détails

ID Serval
serval:BIB_D780B198F164
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Thymic stromal lymphopoietin plays divergent roles in murine models of atopic and nonatopic airway inflammation.
Périodique
Allergy
Auteur(s)
Yadava K., Massacand J., Mosconi I., Nicod L.P., Harris N.L., Marsland B.J.
ISSN
1398-9995 (Electronic)
ISSN-L
0105-4538
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
69
Numéro
10
Pages
1333-1342
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a cytokine primarily produced by epithelial cells, which has been shown to be a potent inducer of T-helper 2 (Th2)-type responses. However, TSLP has pleiotropic effects upon immune cells, and although extensively studied in the context of atopic asthma, its relevance as a therapeutic target and its role in the pathogenesis of nonatopic asthma remains unknown. We sought to investigate the role of TSLP in atopic, nonatopic and viral-induced exacerbations of pulmonary inflammation.
METHODS: Using stringently defined murine models of atopic, nonatopic and virally exacerbated forms of pulmonary inflammation, we compared inflammatory responses of C57BL/6 wild-type (WT) and TSLP receptor-deficient (TSLPR KO) mice.
RESULTS: Thymic stromal lymphopoietin receptor (TSLPR) signaling was crucial for the development of atopic asthma. Specifically, TSLPR signaling to lung recruited CD4+ T cells enhanced eosinophilia, goblet cell hyperplasia, and overall inflammation within the airways. In contrast, the absence of TSLPR signaling was associated with strikingly exaggerated pulmonary neutrophilic inflammation in a nonatopic model of airway inflammation. The inflammation was associated with excessive levels of interleukin (IL)-17A in the lungs, indicating that TSLP negatively regulates IL-17A. In addition, in a model of influenza-induced exacerbation of atopic airway inflammation, the absence of TSLPR signaling also led to exaggerated neutrophilic inflammation.
CONCLUSION: Thymic stromal lymphopoietin plays divergent roles in the pathogenesis of atopic and nonatopic asthma phenotypes by either enhancing Th2 responses or curtailing T-helper 17 responses. These findings raise important caveats for the design of therapeutic interventions targeting TSLP in asthma.
Pubmed
Web of science
Création de la notice
06/11/2014 20:09
Dernière modification de la notice
20/08/2019 16:57
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