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

Details

Serval ID
serval:BIB_0E86E32D15D8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Allergen-induced IgE-dependent gut inflammation in a human PBMC-engrafted murine model of allergy.
Journal
Journal of Allergy and Clinical Immunology
Author(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
Publication state
Published
Issued date
2012
Volume
129
Number
4
Pages
1126-1135
Language
english
Notes
Publication types: Journal Article
Abstract
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
Create date
28/04/2012 8:41
Last modification date
20/08/2019 12:35
Usage data