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Lookup NU author(s): Dr Kile GreenORCiD, Katie Best, 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
Year: 2018
Volume: 19
Pages: 859-870
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
URL: https://doi.org/10.1038/s41590-018-0161-8
DOI: 10.1038/s41590-018-0161-8
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