Nature immunology, 2018-08, Vol.19 (8), p.859
2018
Details
- Autor(en) / Beteiligte
- Titel
- Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response
- Ist Teil von
- Nature immunology, 2018-08, Vol.19 (8), p.859
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1529-2916DOI: 10.1038/s41590-018-0161-8Titel-ID: cdi_pubmed_primary_30013146
- Format
- –
- Schlagworte
- 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