Titre
Thymic stromal lymphopoietin plays divergent roles in murine models of atopic and nonatopic airway inflammation.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Yadava, K.
Auteure/Auteur
Massacand, J.
Auteure/Auteur
Mosconi, I.
Auteure/Auteur
Nicod, L.P.
Auteure/Auteur
Harris, N.L.
Auteure/Auteur
Marsland, B.J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1398-9995
Statut éditorial
Publié
Date de publication
2014
Volume
69
Numéro
10
Première page
1333
Dernière page/numéro d’article
1342
Peer-reviewed
Oui
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.
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.
PID Serval
serval:BIB_D780B198F164
PMID
Date de création
2014-11-06T18:09:42.440Z
Date de création dans IRIS
2025-05-20T22:28:33Z