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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 |