IgE is the least abundant circulating antibody class but is constitutively present in healthy tissues bound to resident cells via its high-affinity receptor, FcεRI. The physiological role of endogenous IgE antibodies is unclear but it has been suggested that they provide host protection against a variety of noxious environmental substances and parasitic infections at epithelial barrier surfaces. Here we show, in mice, that skin inflammation enhances levels of IgE antibodies that have natural specificities and a repertoire, VDJ rearrangements and CDRH3 characteristics similar to those of IgE antibodies in healthy tissue. IgE-bearing basophils are recruited to inflamed skin via CXCL12 and thymic stromal lymphopoietin (TSLP)/IL-3-dependent upregulation of CXCR4. In the inflamed skin, IgE/FcεRI-signalling in basophils promotes epithelial cell growth and differentiation, partly through histamine engagement of H₁R and H₄R. Furthermore, this IgE response strongly drives tumour outgrowth of epithelial cells harbouring oncogenic mutation. These findings indicate that natural IgE antibodies support skin barrier defences, but that during chronic tissue inflammation this role may be subverted to promote tumour growth.

中文翻译：

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炎症诱导的IgE促进上皮增生和肿瘤生长

IgE是循环抗体中含量最少的类别，但通过其高亲和力受体FcεRI组成成分存在于与驻留细胞结合的健康组织中。内源性IgE抗体的生理作用尚不清楚，但已建议它们为上皮屏障表面的各种有害环境物质和寄生虫感染提供宿主保护。在这里，我们表明，在小鼠中，皮肤炎症会增强具有天然特异性的IgE抗体的水平，并且与健康组织中的IgE抗体具有相似的库，VDJ重排和CDRH3特征。通过CXCL12和CXCR4的胸腺基质淋巴细胞生成素（TSLP）/ IL-3依赖性上调，将IgE嗜碱性粒细胞募集到发炎的皮肤。在发炎的皮肤中₁，R和h ₄ R.此外，该IgE应答强烈驱动上皮细胞窝藏致癌突变的肿瘤生长。这些发现表明，天然IgE抗体支持皮肤屏障防御，但在慢性组织炎症过程中，该作用可能被颠覆以促进肿瘤生长。