Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice.

6533b7d7fe1ef96bd1267c6e

RESEARCH PRODUCT

Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice.

Benno Weigmann Ari Waisman Iris Bellinghausen Joachim Saloga Melanie Eschborn Sonja Reissig

subject

CD4-Positive T-Lymphocytes Male medicine.medical_treatment Immunology Inflammation Nod Mice SCID Biology Immunoglobulin E T-Lymphocytes Regulatory Mice medicine Hypersensitivity Immunology and Allergy Animals Humans IL-2 receptor Antibodies Blocking Cells Cultured Cell Proliferation Immunosuppression Therapy Inflammation Severe combined immunodeficiency Interleukin-2 Receptor alpha Subunit Membrane Proteins hemic and immune systems Forkhead Transcription Factors Dendritic cell Allergens Immunoglobulin E medicine.disease Intestines Disease Models Animal Cytokine Immunology Humanized mouse Antibody Formation CD4 Antigens biology.protein Leukocytes Mononuclear Female medicine.symptom

description

Background Recently, we developed a humanized mouse model of allergen-induced IgE-dependent gut inflammation in PBMC-engrafted immunodeficient mice. Objective In the present study, we wanted to investigate the role of regulatory T (Treg) cells and their activation status in this model. Methods Nonobese diabetic-severe combined immunodeficiency-γc −/− 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. Results 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. Conclusions 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.

year	journal	country	edition	language
2015-07-01	The Journal of allergy and clinical immunology

10.1016/j.jaci.2015.04.020 https://pubmed.ncbi.nlm.nih.gov/26145987