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

Greg Crawford; Mark David Hayes; Rocio Castro Seoane; Sophie Ward; Tim Dalessandri; Chester Lai; Eugene  Healy; David Kipling; Charlotte Proby; Colin Moyes; Kile Green; Katie Best; Muzlifah Haniffa; Marina Botto; Deborah Dunn-Walters; Jessica Strid

doi:10.1038/s41590-018-0161-8

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

Greg Crawford, Mark David Hayes, Rocio Castro Seoane, Sophie Ward, Tim Dalessandri, Chester Lai, Eugene Healy, David Kipling, Charlotte Proby, Colin Moyes, Kile Green, Katie Best, Muzlifah Haniffa, Marina Botto, Deborah Dunn-Walters, Jessica Strid (Lead / Corresponding author)

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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 squamouscell 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.

Original language	English
Pages (from-to)	859-870
Number of pages	12
Journal	Nature Immunology
Volume	19
Issue number	8
DOIs	https://doi.org/10.1038/s41590-018-0161-8
Publication status	Published - 16 Jul 2018

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/s41590-018-0161-8

Author Accepted Manuscript
The final publication, ‘Epithelial damage and tissue γδ T cells promote a unique tumorprotectiveIgE response’, Nature Immunology 19:8 (2018): 859–870, is available at http://dx.doi.org/10.1038/s41590-018-0161-8
Accepted author manuscript, 288 KB

Proby, Charlotte
- Cancer Research - Professor (Research Only) of Dermatology
Person: Academic

Cite this

Crawford, G., Hayes, M. D., Seoane, R. C., Ward, S., Dalessandri, T., Lai, C., Healy, E., Kipling, D., Proby, C., Moyes, C., Green, K., Best, K., Haniffa, M., Botto, M., Dunn-Walters, D., & Strid, J. (2018). Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response. Nature Immunology, 19(8), 859-870. https://doi.org/10.1038/s41590-018-0161-8

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title = "Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response",

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 squamouscell 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.",

author = "Greg Crawford and Hayes, {Mark David} and Seoane, {Rocio Castro} and Sophie Ward and Tim Dalessandri and Chester Lai and Eugene Healy and David Kipling and Charlotte Proby and Colin Moyes and Kile Green and Katie Best and Muzlifah Haniffa and Marina Botto and Deborah Dunn-Walters and Jessica Strid",

note = "This work was supported by the Wellcome Trust (100999/Z/13/Z) and in part by the Cancer Research UK (C21010/A19788) and the NIHR Newcastle Biomedical Research Centre. C.L. was supported by a Wellcome Trust Research Training Fellowship.",

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AU - Crawford, Greg

AU - Hayes, Mark David

AU - Seoane, Rocio Castro

AU - Ward, Sophie

AU - Dalessandri, Tim

AU - Lai, Chester

AU - Healy, Eugene

AU - Kipling, David

AU - Proby, Charlotte

AU - Moyes, Colin

AU - Green, Kile

AU - Best, Katie

AU - Haniffa, Muzlifah

AU - Botto, Marina

AU - Dunn-Walters, Deborah

AU - Strid, Jessica

N1 - This work was supported by the Wellcome Trust (100999/Z/13/Z) and in part by the Cancer Research UK (C21010/A19788) and the NIHR Newcastle Biomedical Research Centre. C.L. was supported by a Wellcome Trust Research Training Fellowship.

PY - 2018/7/16

Y1 - 2018/7/16

N2 - 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 squamouscell 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.

AB - 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 squamouscell 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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DO - 10.1038/s41590-018-0161-8

M3 - Article

C2 - 30013146

SN - 1529-2908

VL - 19

SP - 859

EP - 870

JO - Nature Immunology

JF - Nature Immunology

IS - 8

ER -

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

Abstract

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UN SDGs

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Proby, Charlotte

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