Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice
Eschborn M, Weigmann B, Reissig S, Waisman A, Saloga J, Bellinghausen I (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 136
Pages Range: 159-68
Journal Issue: 1
DOI: 10.1016/j.jaci.2015.04.020
Abstract
Recently, we developed a humanized mouse model of allergen-induced IgE-dependent gut inflammation in PBMC-engrafted immunodeficient mice.In the present study, we wanted to investigate the role of regulatory T (Treg) cells and their activation status in this model.Nonobese diabetic-severe combined immunodeficiency-?c(-/-) mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or NaCl as control in the presence or absence of different concentrations of CD4(+)CD25(+) Treg cells of the same donor. After an additional allergen boost 1 week later, mice were challenged with the allergen rectally on day 21 and gut inflammation was monitored by a high-resolution video mini-endoscopic system evaluating translucency, granularity, fibrin production, vascularity, and stool.Allergen-specific human IgE in mouse sera, which was detectable only in PBMC plus allergen-treated mice, was strongly inhibited by coinjection of Treg cells at a ratio of at least 1:10. Consequently, the presence of Treg cells significantly decreased IgE-dependent allergen-induced gut inflammation after rectal allergen challenge. In addition, Treg cells reduced allergen-specific proliferation and cytokine production of recovered human CD4(+) T cells in vitro. Activation of Treg cells before injection further increased all inhibitory effects. Prevention of gut inflammation also occurred by the administration of glycoprotein A repetitions predominant, a molecule expressed by activated Treg cells, whereas its blockade completely abrogated inhibition by Treg cells.These results demonstrate that allergen-specific gut inflammation in human PBMC-engrafted mice can be avoided by enhancing the numbers or activity of autologous Treg cells, which is of great interest for therapeutic intervention of allergic diseases of the intestine.
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Germany (DE)How to cite
APA:
Eschborn, M., Weigmann, B., Reissig, S., Waisman, A., Saloga, J., & Bellinghausen, I. (2015). Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice. Journal of Allergy and Clinical Immunology, 136(1), 159-68. https://doi.org/10.1016/j.jaci.2015.04.020
MLA:
Eschborn, Melanie, et al. "Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice." Journal of Allergy and Clinical Immunology 136.1 (2015): 159-68.
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