IgE-activated mast cells enhance TLR4-mediated antigen-specific CD4+ T cell responses

Abstract Mast cells are potent mediators of allergy and asthma, yet their role in regulating adaptive immunity remains ambiguous. On the surface of mast cells, the crosslinking of IgE bound to FcεRI by a specific antigen recognized by that IgE triggers the release of immune mediators such as histami...

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Main Authors: Binh L. Phong, Shaina J. D’Souza, Robin L. Baudier, Eric Wu, Victoria E. Immethun, David L. Bauer, James B. McLachlan
Format: Article
Language:English
Published: Nature Publishing Group 2021-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-88956-4
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spelling doaj-32e9ca69d1884b0986078bf9e44648192021-05-09T11:32:31ZengNature Publishing GroupScientific Reports2045-23222021-05-0111111310.1038/s41598-021-88956-4IgE-activated mast cells enhance TLR4-mediated antigen-specific CD4+ T cell responsesBinh L. Phong0Shaina J. D’Souza1Robin L. Baudier2Eric Wu3Victoria E. Immethun4David L. Bauer5James B. McLachlan6Department of Microbiology and Immunology, Tulane University School of MedicineDepartment of Microbiology and Immunology, Tulane University School of MedicineDepartment of Epidemiology, Tulane University School of Public Health and Tropical MedicineDepartment of Biochemistry and Molecular Biology, Tulane University School of MedicineDepartment of Microbiology and Immunology, Tulane University School of MedicineDepartment of Microbiology and Immunology, Tulane University School of MedicineDepartment of Microbiology and Immunology, Tulane University School of MedicineAbstract Mast cells are potent mediators of allergy and asthma, yet their role in regulating adaptive immunity remains ambiguous. On the surface of mast cells, the crosslinking of IgE bound to FcεRI by a specific antigen recognized by that IgE triggers the release of immune mediators such as histamine and cytokines capable of activating other immune cells; however, little is known about the mast cell contribution to the induction of endogenous, antigen-specific CD4+ T cells. Here we examined the effects of specific mast cell activation in vivo on the initiation of an antigen-specific CD4+ T cell response. While CD4+ T cells were not enhanced by FcεRI stimulation alone, their activation was synergistically enhanced when FcεRI activation was combined with TLR4 stimulation. This enhanced activation was dependent on global TLR4 stimulation but appeared to be less dependent on mast cell expressed TLR4. This study provides important new evidence to support the role of mast cells as mediators of the antigen-specific adaptive immune response.https://doi.org/10.1038/s41598-021-88956-4
collection DOAJ
language English
format Article
sources DOAJ
author Binh L. Phong
Shaina J. D’Souza
Robin L. Baudier
Eric Wu
Victoria E. Immethun
David L. Bauer
James B. McLachlan
spellingShingle Binh L. Phong
Shaina J. D’Souza
Robin L. Baudier
Eric Wu
Victoria E. Immethun
David L. Bauer
James B. McLachlan
IgE-activated mast cells enhance TLR4-mediated antigen-specific CD4+ T cell responses
Scientific Reports
author_facet Binh L. Phong
Shaina J. D’Souza
Robin L. Baudier
Eric Wu
Victoria E. Immethun
David L. Bauer
James B. McLachlan
author_sort Binh L. Phong
title IgE-activated mast cells enhance TLR4-mediated antigen-specific CD4+ T cell responses
title_short IgE-activated mast cells enhance TLR4-mediated antigen-specific CD4+ T cell responses
title_full IgE-activated mast cells enhance TLR4-mediated antigen-specific CD4+ T cell responses
title_fullStr IgE-activated mast cells enhance TLR4-mediated antigen-specific CD4+ T cell responses
title_full_unstemmed IgE-activated mast cells enhance TLR4-mediated antigen-specific CD4+ T cell responses
title_sort ige-activated mast cells enhance tlr4-mediated antigen-specific cd4+ t cell responses
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-05-01
description Abstract Mast cells are potent mediators of allergy and asthma, yet their role in regulating adaptive immunity remains ambiguous. On the surface of mast cells, the crosslinking of IgE bound to FcεRI by a specific antigen recognized by that IgE triggers the release of immune mediators such as histamine and cytokines capable of activating other immune cells; however, little is known about the mast cell contribution to the induction of endogenous, antigen-specific CD4+ T cells. Here we examined the effects of specific mast cell activation in vivo on the initiation of an antigen-specific CD4+ T cell response. While CD4+ T cells were not enhanced by FcεRI stimulation alone, their activation was synergistically enhanced when FcεRI activation was combined with TLR4 stimulation. This enhanced activation was dependent on global TLR4 stimulation but appeared to be less dependent on mast cell expressed TLR4. This study provides important new evidence to support the role of mast cells as mediators of the antigen-specific adaptive immune response.
url https://doi.org/10.1038/s41598-021-88956-4
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