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Lookup NU author(s): Dr Kile GreenORCiD,
Professor Muzlifah Haniffa
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2018.
For re-use rights please refer to the publisher's terms and conditions.
© 2018 The Author(s) 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.
Author(s): Crawford G, Hayes MD, Seoane RC, Ward S, Dalessandri T, Lai C, Healy E, Kipling D, Proby C, Moyes C, Green K, Best K, Haniffa M, Botto M, Dunn-Walters D, Strid J
Publication type: Article
Publication status: Published
Journal: Nature Immunology
Online publication date: 16/07/2018
Acceptance date: 02/04/2018
Date deposited: 21/02/2019
ISSN (print): 1529-2908
ISSN (electronic): 1529-2916
Publisher: Nature Publishing Group
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