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Regulatory CD4(+)Foxp3(+) T Cells Control the Severity of Anaphylaxis

OBJECTIVE: Anaphylaxis is a life-threatening outcome of immediate-type hypersensitivity to allergen, consecutive to mast cell degranulation by allergen-specific IgE. Regulatory T cells (Treg) can control allergic sensitization and mast cell degranulation, yet their clinical benefit on anaphylactic s...

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Autores principales: Kanjarawi, Reem, Dy, Michel, Bardel, Emilie, Sparwasser, Tim, Dubois, Bertrand, Mecheri, Salah, Kaiserlian, Dominique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724852/
https://www.ncbi.nlm.nih.gov/pubmed/23922690
http://dx.doi.org/10.1371/journal.pone.0069183
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author Kanjarawi, Reem
Dy, Michel
Bardel, Emilie
Sparwasser, Tim
Dubois, Bertrand
Mecheri, Salah
Kaiserlian, Dominique
author_facet Kanjarawi, Reem
Dy, Michel
Bardel, Emilie
Sparwasser, Tim
Dubois, Bertrand
Mecheri, Salah
Kaiserlian, Dominique
author_sort Kanjarawi, Reem
collection PubMed
description OBJECTIVE: Anaphylaxis is a life-threatening outcome of immediate-type hypersensitivity to allergen, consecutive to mast cell degranulation by allergen-specific IgE. Regulatory T cells (Treg) can control allergic sensitization and mast cell degranulation, yet their clinical benefit on anaphylactic symptoms is poorly documented. Here we investigated whether Treg action during the effector arm of the allergic response alleviates anaphylaxis. METHODS: We used a validated model of IgE-mediated passive systemic anaphylaxis, induced by intravenous challenge with DNP-HSA in mice passively sensitized with DNP-specific IgE. Anaphylaxis was monitored by the drop in body temperature as well as plasma histamine and serum mMCP1 levels. The role of Treg was analyzed using MHC class II-deficient (Aβ(°/°)) mice, treatment with anti-CD25 or anti-CD4 mAbs and conditional ablation of Foxp3(+) Treg in DEREG mice. Therapeutic efficacy of Treg was also evaluated by transfer experiments using FoxP3-eGFP knock-in mice. RESULTS: Anaphylaxis did not occur in mast cell-deficient W/W(v) mutant mice and was only moderate and transient in mice deficient for histamine receptor-1. Defects in constitutive Treg, either genetic or induced by antibody or toxin treatment resulted in a more severe and/or sustained hypothermia, associated with a rise in serum mMCP1, but not histamine. Adoptive transfer of Foxp3(+) Treg from either naïve or DNP-sensitized donors similarly alleviated body temperature loss in Treg-deficient DEREG mice. CONCLUSION: Constitutive Foxp3(+) Treg can control the symptomatic phase of mast cell and IgE-dependent anaphylaxis in mice. This might open up new therapeutic avenues using constitutive rather than Ag-specific Treg for inducing tolerance in allergic patients.
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spelling pubmed-37248522013-08-06 Regulatory CD4(+)Foxp3(+) T Cells Control the Severity of Anaphylaxis Kanjarawi, Reem Dy, Michel Bardel, Emilie Sparwasser, Tim Dubois, Bertrand Mecheri, Salah Kaiserlian, Dominique PLoS One Research Article OBJECTIVE: Anaphylaxis is a life-threatening outcome of immediate-type hypersensitivity to allergen, consecutive to mast cell degranulation by allergen-specific IgE. Regulatory T cells (Treg) can control allergic sensitization and mast cell degranulation, yet their clinical benefit on anaphylactic symptoms is poorly documented. Here we investigated whether Treg action during the effector arm of the allergic response alleviates anaphylaxis. METHODS: We used a validated model of IgE-mediated passive systemic anaphylaxis, induced by intravenous challenge with DNP-HSA in mice passively sensitized with DNP-specific IgE. Anaphylaxis was monitored by the drop in body temperature as well as plasma histamine and serum mMCP1 levels. The role of Treg was analyzed using MHC class II-deficient (Aβ(°/°)) mice, treatment with anti-CD25 or anti-CD4 mAbs and conditional ablation of Foxp3(+) Treg in DEREG mice. Therapeutic efficacy of Treg was also evaluated by transfer experiments using FoxP3-eGFP knock-in mice. RESULTS: Anaphylaxis did not occur in mast cell-deficient W/W(v) mutant mice and was only moderate and transient in mice deficient for histamine receptor-1. Defects in constitutive Treg, either genetic or induced by antibody or toxin treatment resulted in a more severe and/or sustained hypothermia, associated with a rise in serum mMCP1, but not histamine. Adoptive transfer of Foxp3(+) Treg from either naïve or DNP-sensitized donors similarly alleviated body temperature loss in Treg-deficient DEREG mice. CONCLUSION: Constitutive Foxp3(+) Treg can control the symptomatic phase of mast cell and IgE-dependent anaphylaxis in mice. This might open up new therapeutic avenues using constitutive rather than Ag-specific Treg for inducing tolerance in allergic patients. Public Library of Science 2013-07-26 /pmc/articles/PMC3724852/ /pubmed/23922690 http://dx.doi.org/10.1371/journal.pone.0069183 Text en © 2013 kanjarawi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kanjarawi, Reem
Dy, Michel
Bardel, Emilie
Sparwasser, Tim
Dubois, Bertrand
Mecheri, Salah
Kaiserlian, Dominique
Regulatory CD4(+)Foxp3(+) T Cells Control the Severity of Anaphylaxis
title Regulatory CD4(+)Foxp3(+) T Cells Control the Severity of Anaphylaxis
title_full Regulatory CD4(+)Foxp3(+) T Cells Control the Severity of Anaphylaxis
title_fullStr Regulatory CD4(+)Foxp3(+) T Cells Control the Severity of Anaphylaxis
title_full_unstemmed Regulatory CD4(+)Foxp3(+) T Cells Control the Severity of Anaphylaxis
title_short Regulatory CD4(+)Foxp3(+) T Cells Control the Severity of Anaphylaxis
title_sort regulatory cd4(+)foxp3(+) t cells control the severity of anaphylaxis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724852/
https://www.ncbi.nlm.nih.gov/pubmed/23922690
http://dx.doi.org/10.1371/journal.pone.0069183
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