Dermatitis is often associated with an allergic reaction characterized by excessive type 2 responses leading to epidermal acanthosis, hyperkeratosis, and dermal inflammation. Although factors like IL-4, IL-13, and thymic stromal lymphopoietin (TSLP) are thought to be instrumental for the development of this type of skin disorder, other cytokines may be critical. Here, we show that the tumor necrosis factor (TNF) superfamily protein LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes) is required for experimental atopic dermatitis, and LIGHT directly controls keratinocyte hyperplasia, and production of periostin, a matricellular protein that contributes to the clinical features of atopic dermatitis as well as other skin diseases such as scleroderma. Mice with a conditional deletion of the LIGHT receptor HVEM (herpesvirus entry mediator) in keratinocytes phenocopied LIGHT-deficient mice in exhibiting reduced epidermal thickening and dermal collagen deposition in a model of atopic dermatitis driven by house dust mite allergen. LIGHT signaling through HVEM in human epidermal keratinocytes directly induced proliferation and periostin expression, and both keratinocyte-specific deletion of HVEM or antibody blocking of LIGHT–HVEM interactions after disease onset prevented expression of periostin and limited atopic dermatitis symptoms. Developing reagents that neutralize LIGHT–HVEM signaling might be useful for therapeutic intervention in skin diseases where periostin is a central feature.

皮炎通常与过敏反应有关，其特征是过度的 2 型反应导致表皮棘层肥厚、角化过度和皮肤炎症。虽然 IL-4、IL-13 和胸腺基质淋巴细胞生成素 (TSLP) 等因素被认为有助于此类皮肤病的发展，但其他细胞因子可能至关重要。在这里，我们表明肿瘤坏死因子 (TNF) 超家族蛋白 LIGHT（与淋巴毒素同源，表现出可诱导表达，并与 HSV 糖蛋白 D 竞争结合 HVEM，一种在 T 淋巴细胞上表达的受体）是实验性特应性皮炎所必需的，并且LIGHT 直接控制角质形成细胞增生和骨膜素的产生，一种基质细胞蛋白，可导致特应性皮炎以及其他皮肤病（如硬皮病）的临床特征。在由屋尘螨过敏原驱动的特应性皮炎模型中，角质形成细胞中 LIGHT 受体 HVEM（疱疹病毒进入介质）条件性缺失的小鼠对 LIGHT 缺陷小鼠表现出减少的表皮增厚和真皮胶原沉积。通过人表皮角质形成细胞中的 HVEM 进行的 LIGHT 信号传导直接诱导增殖和骨膜素表达，并且在疾病发作后角质形成细胞特异性缺失 HVEM 或抗体阻断 LIGHT-HVEM 相互作用都阻止了骨膜素的表达并限制了特应性皮炎症状。