Psoriasis (PS) and atopic dermatitis (AD) are common skin inflammatory diseases characterized by hyper-responsive keratinocytes. Although, some cytokines have been suggested to be specific for each disease, other cytokines might be central to both diseases. Here, we show that Tumor necrosis factor superfamily member 14 (TNFSF14), known as LIGHT, is required for experimental PS, similar to its requirement in experimental AD. Mice devoid of LIGHT, or deletion of either of its receptors, lymphotoxin β receptor (LTβR) and herpesvirus entry mediator (HVEM), in keratinocytes, were protected from developing imiquimod-induced psoriatic features, including epidermal thickening and hyperplasia, and expression of PS-related genes. Correspondingly, in single cell RNA-seq analysis of PS patient biopsies, LTβR transcripts were found strongly expressed with HVEM in keratinocytes, and LIGHT was upregulated in T cells. Similar transcript expression profiles were also seen in AD biopsies, and LTβR deletion in keratinocytes also protected mice from allergen-induced AD features. Moreover, in vitro, LIGHT upregulated a broad spectrum of genes in human keratinocytes that are clinical features of both PS and AD skin lesions. Our data suggest that agents blocking LIGHT activity might be useful for therapeutic intervention in PS as well as in AD.

中文翻译：

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角质形成细胞中通过 LTβR 和 HVEM 发出的光信号可促进牛皮癣和特应性皮炎样皮肤炎症

银屑病（PS）和特应性皮炎（AD）是常见的皮肤炎症性疾病，其特征是角质形成细胞高反应性。尽管某些细胞因子被认为对每种疾病具有特异性，但其他细胞因子可能是这两种疾病的核心。在这里，我们表明肿瘤坏死因子超家族成员 14 (TNFSF14)（称为 LIGHT）是实验 PS 所必需的，类似于实验 AD 中的要求。角质形成细胞中缺乏 LIGHT 或缺失其任一受体、淋巴毒素 β 受体 (LTβR) 和疱疹病毒进入介质 (HVEM) 的小鼠，可以避免出现咪喹莫特诱导的银屑病特征，包括表皮增厚和增生以及 PS 表达相关基因。相应地，在 PS 患者活检组织的单细胞 RNA-seq 分析中，发现 LTβR 转录物在角质形成细胞中与 HVEM 强烈表达，并且 LIGHT 在 T 细胞中上调。 AD 活检中也发现了类似的转录本表达谱，角质形成细胞中 LTβR 的缺失也保护小鼠免受过敏原诱导的 AD 特征。此外，在体外，LIGHT 上调了人类角质形成细胞中的多种基因，这些基因是 PS 和 AD 皮肤病变的临床特征。我们的数据表明，阻断 LIGHT 活性的药物可能有助于 PS 和 AD 的治疗干预。