Allergen-induced IgE-dependent gut inflammation in a human PBMC-engrafted murine model of allergy.

Détails

ID Serval
serval:BIB_0E86E32D15D8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Allergen-induced IgE-dependent gut inflammation in a human PBMC-engrafted murine model of allergy.
Périodique
Journal of Allergy and Clinical Immunology
Auteur(s)
Weigmann B., Schughart N., Wiebe C., Sudowe S., Lehr H.A., Jonuleit H., Vogel L., Becker C., Neurath M.F., Grabbe S., Saloga J., Bellinghausen I.
ISSN
1097-6825 (Electronic)
ISSN-L
0091-6749
Statut éditorial
Publié
Date de publication
2012
Volume
129
Numéro
4
Pages
1126-1135
Langue
anglais
Notes
Publication types: Journal Article
Résumé
BACKGROUND: Humanized murine models comprise a new tool to analyze novel therapeutic strategies for allergic diseases of the intestine.¦OBJECTIVE: In this study we developed a human PBMC-engrafted murine model of allergen-driven gut inflammation and analyzed the underlying immunologic mechanisms.¦METHODS: Nonobese diabetic (NOD)-scid-γc(-/-) mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or not. Three weeks later, mice were challenged with the allergen orally or rectally, and gut inflammation was monitored with a high-resolution video miniendoscopic system, as well as histologically.¦RESULTS: Using the aeroallergens birch or grass pollen as model allergens and, for some donors, also hazelnut allergen, we show that allergen-specific human IgE in murine sera and allergen-specific proliferation and cytokine production of human CD4(+) T cells recovered from spleens after 3 weeks could only be measured in mice treated with PBMCs plus allergen. Importantly, these mice had the highest endoscopic scores evaluating translucent structure, granularity, fibrin, vascularity, and stool after oral or rectal allergen challenge and a strong histologic inflammation of the colon. Analyzing the underlying mechanisms, we demonstrate that allergen-associated colitis was dependent on IgE, human IgE receptor-expressing effector cells, and the mediators histamine and platelet-activating factor.¦CONCLUSION: These results demonstrate that allergic gut inflammation can be induced in human PBMC-engrafted mice, allowing the investigation of pathophysiologic mechanisms of allergic diseases of the intestine and evaluation of therapeutic interventions.
Pubmed
Web of science
Création de la notice
28/04/2012 9:41
Dernière modification de la notice
20/08/2019 13:35
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