Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response.
Nat Immunol
; 19(8): 859-870, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-30013146
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Imunoglobulina E
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Linfócitos B
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Carcinoma de Células Escamosas
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Receptores de Antígenos de Linfócitos T gama-delta
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Receptores de IgE
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Células Epiteliais
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Linfócitos Intraepiteliais
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Neoplasias Experimentais
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido