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

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Title: Epithelial damage and tissue gamma delta T cells promote a unique tumor-protective IgE response
Authors: 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
Item Type: Journal 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.
Issue Date: 16-Jul-2018
Date of Acceptance: 12-Jun-2018
URI: http://hdl.handle.net/10044/1/61794
DOI: 10.1038/s41590-018-0161-8
ISSN: 1529-2908
Publisher: Nature Research
Start Page: 859
End Page: 870
Journal / Book Title: Nature Immunology
Volume: 19
Issue: 8
Copyright Statement: © 2018 Springer Nature Limited. All rights reserved. The final publication is available at https://dx.doi.org/10.1038/s41590-018-0161-8
Sponsor/Funder: Wellcome Trust
Cancer Research UK
Funder's Grant Number: 100999/Z/13/Z
19788
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
NONMELANOMA SKIN-CANCER
IMMUNOGLOBULIN-E
REPERTOIRE
DIVERSITY
GENES
MICE
AUTOANTIBODIES
SURVEILLANCE
AUTOIMMUNITY
ANAPHYLAXIS
Animals
Anthracenes
B-Lymphocytes
Carcinoma, Squamous Cell
Cell Death
Cells, Cultured
Complementarity Determining Regions
DNA Damage
Epithelial Cells
Female
High-Throughput Nucleotide Sequencing
Immunoglobulin Class Switching
Immunoglobulin E
Immunologic Surveillance
Intraepithelial Lymphocytes
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasms, Experimental
Piperidines
Prognosis
Receptors, Antigen, T-Cell, gamma-delta
Receptors, IgE
B-Lymphocytes
Cells, Cultured
Epithelial Cells
Animals
Mice, Inbred C57BL
Mice, Knockout
Mice
Carcinoma, Squamous Cell
Neoplasms, Experimental
DNA Damage
Piperidines
Anthracenes
Immunoglobulin E
Complementarity Determining Regions
Receptors, Antigen, T-Cell, gamma-delta
Receptors, IgE
Prognosis
Cell Death
Immunologic Surveillance
Immunoglobulin Class Switching
Female
High-Throughput Nucleotide Sequencing
Intraepithelial Lymphocytes
Science & Technology
Life Sciences & Biomedicine
Immunology
NONMELANOMA SKIN-CANCER
IMMUNOGLOBULIN-E
DEFICIENT MICE
ALLERGIC SENSITIZATION
ATOPIC-DERMATITIS
AIR-POLLUTION
AUTOIMMUNITY
GENES
REPERTOIRE
DIVERSITY
1107 Immunology
Immunology
Publication Status: Published
Online Publication Date: 2018-07-16
Appears in Collections:Department of Immunology and Inflammation
Department of Metabolism, Digestion and Reproduction
Faculty of Medicine