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Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response

Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response
Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response
IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by γδTCR+ intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that γδ T cells shaped the IgE repertoire by supporting specific variable-diversity-joining (VDJ) rearrangements with unique characteristics of the complementarity-determining region CDRH3. This endogenous IgE response, via the IgE receptor FcεRI, provided protection against epithelial carcinogenesis, and expression of the gene encoding FcεRI in human squamous-cell carcinoma correlated with good disease prognosis. These data indicate a joint role for immunosurveillance by T cells and by B cells in epithelial tissues and suggest that IgE is part of the host defense against epithelial damage and tumor development.
1529-2908
859-870
Crawford, Greg
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Hayes, Mark David
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Seoane, Rocio Castro
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Ward, Sophie
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Dalessandri, Tim
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Lai, Chester
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Healy, Eugene
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Kipling, David
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Proby, Charlotte
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Moyes, Colin
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Green, Kile
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Best, Katie
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Haniffa, Muzlifah
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Botto, Marina
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Dunn-Walters, Deborah
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Strid, Jessica
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Crawford, Greg
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Hayes, Mark David
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Seoane, Rocio Castro
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Ward, Sophie
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Dalessandri, Tim
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Lai, Chester
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Healy, Eugene
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Kipling, David
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Proby, Charlotte
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Moyes, Colin
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Green, Kile
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Best, Katie
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Haniffa, Muzlifah
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Botto, Marina
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Dunn-Walters, Deborah
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Strid, Jessica
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Crawford, Greg, Hayes, Mark David, Seoane, Rocio Castro, Ward, Sophie, Dalessandri, Tim, Lai, Chester, Healy, Eugene, Kipling, David, Proby, Charlotte, Moyes, Colin, Green, Kile, Best, Katie, Haniffa, Muzlifah, Botto, Marina, Dunn-Walters, Deborah and Strid, Jessica (2018) Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response. Nature Immunology, 19, 859-870. (doi:10.1038/s41590-018-0161-8).

Record type: Article

Abstract

IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by γδTCR+ intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that γδ T cells shaped the IgE repertoire by supporting specific variable-diversity-joining (VDJ) rearrangements with unique characteristics of the complementarity-determining region CDRH3. This endogenous IgE response, via the IgE receptor FcεRI, provided protection against epithelial carcinogenesis, and expression of the gene encoding FcεRI in human squamous-cell carcinoma correlated with good disease prognosis. These data indicate a joint role for immunosurveillance by T cells and by B cells in epithelial tissues and suggest that IgE is part of the host defense against epithelial damage and tumor development.

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More information

Accepted/In Press date: 12 June 2018
e-pub ahead of print date: 16 July 2018
Published date: August 2018

Identifiers

Local EPrints ID: 422745
URI: http://eprints.soton.ac.uk/id/eprint/422745
ISSN: 1529-2908
PURE UUID: adb70fe7-2d08-4320-8a3d-f402ecdb9db2

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Date deposited: 01 Aug 2018 16:30
Last modified: 26 Nov 2021 06:46

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Contributors

Author: Greg Crawford
Author: Mark David Hayes
Author: Rocio Castro Seoane
Author: Sophie Ward
Author: Tim Dalessandri
Author: Chester Lai
Author: Eugene Healy
Author: David Kipling
Author: Charlotte Proby
Author: Colin Moyes
Author: Kile Green
Author: Katie Best
Author: Muzlifah Haniffa
Author: Marina Botto
Author: Deborah Dunn-Walters
Author: Jessica Strid

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