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, 859-870. (doi:10.1038/s41590-018-0161-8).
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.
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