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

Nat Immunol. 2018 Aug;19(8):859-870. doi: 10.1038/s41590-018-0161-8. Epub 2018 Jul 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthracenes / toxicity
  • B-Lymphocytes / physiology*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / immunology*
  • Cell Death
  • Cells, Cultured
  • Complementarity Determining Regions / genetics
  • DNA Damage
  • Epithelial Cells / physiology*
  • Female
  • High-Throughput Nucleotide Sequencing
  • Immunoglobulin Class Switching
  • Immunoglobulin E / genetics
  • Immunoglobulin E / metabolism*
  • Immunologic Surveillance
  • Intraepithelial Lymphocytes / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasms, Experimental / chemically induced
  • Neoplasms, Experimental / immunology*
  • Piperidines / toxicity
  • Prognosis
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Receptors, IgE / metabolism*


  • 3-(2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino)-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz(a)anthracene
  • Anthracenes
  • Complementarity Determining Regions
  • FcepsilonRIalpha protein, mouse
  • Piperidines
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, IgE
  • Immunoglobulin E