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

Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response.
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DOI:
10.1038/s41590-018-0161-8
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发表时间:
2018-08
期刊:
影响因子:
30.5
通讯作者:
Strid J
Strid J
中科院分区:
医学1区
文献类型:
--
作者:
Crawford G;Hayes MD;Seoane RC;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

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IgE是一种古老而保守的免疫球蛋白同型,具有强大的免疫功能。然而,IgE反应的调控仍然是一个谜,IgE在宿主防御中的作用的证据是有限的。在这里,我们描述了局部暴露于一种常见的环境dna损伤异种生物引发的γδTCR+上皮内淋巴细胞的应激监测,导致B细胞中IgE的类别转换和自身反应性IgE的积累。高通量抗体测序显示,γδ T细胞通过支持具有独特CDRH3特征的特异性VDJ重排来形成IgE库。这种内源性IgE反应,通过fcε - ri,在人类鳞状细胞癌中防止上皮癌变和FceR1a表达,与良好的疾病预后相关。这些数据表明T细胞和B细胞免疫监视在上皮组织中的共同作用,并表明IgE是宿主防御上皮损伤和肿瘤发展的一部分。
IgE is an ancient and conserved immunoglobulin isotype with potent immune function. Nevertheless, the regulation of IgE responses remains enigmatic and evidence for a role of IgE in host defense is limited. Herein we describe that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress-surveillance by γδTCR+ intraepithelial lymphocytes resulting in class-switching to IgE in B cells and accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that γδ T cells shaped the IgE repertoire by supporting specific VDJ rearrangements with unique CDRH3 characteristics. This endogenous IgE response, via the FcεRI, protected against epithelial carcinogenesis and FceR1a expression in human squamous cell carcinoma correlated with good disease prognosis. This data indicate a joint role for T and B cell immune-surveillance in epithelial tissues and suggests that IgE is part of the host defense against epithelial damage and tumor development.
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