上皮细胞衍生的特应性皮炎细胞因子 TSLP 激活神经元以诱导瘙痒。
The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch.
机构信息
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
出版信息
Cell. 2013 Oct 10;155(2):285-95. doi: 10.1016/j.cell.2013.08.057. Epub 2013 Oct 3.
Abstract
Atopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that affects one in ten people. Patients suffering from severe AD eventually progress to develop asthma and allergic rhinitis, in a process known as the "atopic march." Signaling between epithelial cells and innate immune cells via the cytokine thymic stromal lymphopoietin (TSLP) is thought to drive AD and the atopic march. Here, we report that epithelial cells directly communicate to cutaneous sensory neurons via TSLP to promote itch. We identify the ORAI1/NFAT calcium signaling pathway as an essential regulator of TSLP release from keratinocytes, the primary epithelial cells of the skin. TSLP then acts directly on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors. Our results support a model whereby calcium-dependent TSLP release by keratinocytes activates both primary afferent neurons and immune cells to promote inflammatory responses in the skin and airways.
摘要
特应性皮炎（AD）是一种慢性瘙痒和炎症性皮肤疾病，影响十分之一的人群。患有严重 AD 的患者最终会发展为哮喘和过敏性鼻炎，这一过程被称为“特应性进行曲”。细胞因子胸腺基质淋巴细胞生成素（TSLP）在表皮细胞和固有免疫细胞之间的信号传递被认为是导致 AD 和特应性进行曲的原因。在这里，我们报告称，上皮细胞通过 TSLP 与皮肤感觉神经元直接通讯，以促进瘙痒。我们确定 ORAI1/NFAT 钙信号通路是角质形成细胞（皮肤的主要上皮细胞）释放 TSLP 的必需调节剂。然后，TSLP 直接作用于一组 TRPA1 阳性感觉神经元，引发强烈的瘙痒行为。我们的结果支持这样一种模型，即角质形成细胞中钙依赖性 TSLP 释放激活初级传入神经元和免疫细胞，以促进皮肤和气道中的炎症反应。
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