First Author | Crawford G | Year | 2018 |
Journal | Nat Immunol | Volume | 19 |
Issue | 8 | Pages | 859-870 |
PubMed ID | 30013146 | Mgi Jnum | J:282514 |
Mgi Id | MGI:6381130 | Doi | 10.1038/s41590-018-0161-8 |
Citation | Crawford G, et al. (2018) Epithelial damage and tissue gammadelta T cells promote a unique tumor-protective IgE response. Nat Immunol 19(8):859-870 |
abstractText | 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 gammadeltaTCR(+) intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that gammadelta 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 FcepsilonRI, provided protection against epithelial carcinogenesis, and expression of the gene encoding FcepsilonRI 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. |