Escherichia coli Heat-Labile Enterotoxin B Limits T Cells Activation by Promoting Immature Dendritic Cells and Enhancing Regulatory T Cell Function

Treatments to limit T cell activation are essential for managing autoimmune and inflammatory disorders. The B subunit of Escherichia coli heat-labile enterotoxin (EtxB) is known to ameliorate inflammatory disease in vivo but the mechanism by which this is mediated is not well understood. Here, we sh...

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Main Authors: Alexandre Bignon, Alan P. Watt, Michelle A. Linterman
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-05-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fimmu.2017.00560/full
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spelling doaj-42c7003875334038917951b84ae4fe612020-11-24T23:04:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-05-01810.3389/fimmu.2017.00560261256Escherichia coli Heat-Labile Enterotoxin B Limits T Cells Activation by Promoting Immature Dendritic Cells and Enhancing Regulatory T Cell FunctionAlexandre Bignon0Alan P. Watt1Michelle A. Linterman2Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge, UKXenovium Limited, Chesterford Research Park, Little Chesterford, UKLymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge, UKTreatments to limit T cell activation are essential for managing autoimmune and inflammatory disorders. The B subunit of Escherichia coli heat-labile enterotoxin (EtxB) is known to ameliorate inflammatory disease in vivo but the mechanism by which this is mediated is not well understood. Here, we show that following intranasal administration, EtxB acts on two key cellular regulators of T cell activation: regulatory T cells and dendritic cells (DCs). EtxB enhances the proliferation of lung regulatory T cells and doubles their suppressive function, likely through an increase in expression of the Treg effector molecule CTLA-4. EtxB supports the generation of interleukin-10-producing DCs that are unable to activate T cells. These data show, for the first time, that mucosal EtxB treatment limits T cells activation by acting jointly on two distinct types of immune cells.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00560/fullEtxBimmunomodulationlungdendritic cellsregulatory T cells
collection DOAJ
language English
format Article
sources DOAJ
author Alexandre Bignon
Alan P. Watt
Michelle A. Linterman
spellingShingle Alexandre Bignon
Alan P. Watt
Michelle A. Linterman
Escherichia coli Heat-Labile Enterotoxin B Limits T Cells Activation by Promoting Immature Dendritic Cells and Enhancing Regulatory T Cell Function
Frontiers in Immunology
EtxB
immunomodulation
lung
dendritic cells
regulatory T cells
author_facet Alexandre Bignon
Alan P. Watt
Michelle A. Linterman
author_sort Alexandre Bignon
title Escherichia coli Heat-Labile Enterotoxin B Limits T Cells Activation by Promoting Immature Dendritic Cells and Enhancing Regulatory T Cell Function
title_short Escherichia coli Heat-Labile Enterotoxin B Limits T Cells Activation by Promoting Immature Dendritic Cells and Enhancing Regulatory T Cell Function
title_full Escherichia coli Heat-Labile Enterotoxin B Limits T Cells Activation by Promoting Immature Dendritic Cells and Enhancing Regulatory T Cell Function
title_fullStr Escherichia coli Heat-Labile Enterotoxin B Limits T Cells Activation by Promoting Immature Dendritic Cells and Enhancing Regulatory T Cell Function
title_full_unstemmed Escherichia coli Heat-Labile Enterotoxin B Limits T Cells Activation by Promoting Immature Dendritic Cells and Enhancing Regulatory T Cell Function
title_sort escherichia coli heat-labile enterotoxin b limits t cells activation by promoting immature dendritic cells and enhancing regulatory t cell function
publisher Frontiers Media S.A.
series Frontiers in Immunology
issn 1664-3224
publishDate 2017-05-01
description Treatments to limit T cell activation are essential for managing autoimmune and inflammatory disorders. The B subunit of Escherichia coli heat-labile enterotoxin (EtxB) is known to ameliorate inflammatory disease in vivo but the mechanism by which this is mediated is not well understood. Here, we show that following intranasal administration, EtxB acts on two key cellular regulators of T cell activation: regulatory T cells and dendritic cells (DCs). EtxB enhances the proliferation of lung regulatory T cells and doubles their suppressive function, likely through an increase in expression of the Treg effector molecule CTLA-4. EtxB supports the generation of interleukin-10-producing DCs that are unable to activate T cells. These data show, for the first time, that mucosal EtxB treatment limits T cells activation by acting jointly on two distinct types of immune cells.
topic EtxB
immunomodulation
lung
dendritic cells
regulatory T cells
url http://journal.frontiersin.org/article/10.3389/fimmu.2017.00560/full
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