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

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. pp. 859-870.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
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
Strid, Jessica
Date : 16 July 2018
Funders : Wellcome Trust
DOI : 10.1038/s41590-018-0161-8
Copyright Disclaimer : Copyright 2018 The Author(s). Published by Nature Publishing Group
Depositing User : Melanie Hughes
Date Deposited : 18 Jul 2018 11:44
Last Modified : 11 Dec 2018 11:24

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