Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.

中文翻译：

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IL-24 通过驱动 MRSA 诱导的过敏反应来促进特应性皮炎样炎症。


特应性皮炎（AD）是一种常见的炎症性皮肤病，患者会出现反复出现的湿疹皮损和剧烈瘙痒。金黄色葡萄球菌 (S. aureus) 的定植与疾病的严重程度相关，但其在 AD 发展中的作用仍然难以捉摸。通过单细胞 RNA 测序，我们发现角质形成细胞在接触耐甲氧西林金黄色葡萄球菌 (MRSA) 时会激活一种独特的免疫反应，其特征是诱导 Il24。使用动物模型进行的进一步实验表明，施用重组 IL-24 蛋白会使 AD 样病理恶化。角质形成细胞中 Il24 或受体 Il20rb 的基因消除可减轻过敏性炎症和特应性进展。从机制上讲，IL-24 通过其异二聚体受体作用于角质形成细胞，并增加 IL-33 的产生，从而加剧 2 型免疫和 AD 样皮肤状况。总体而言，这些研究结果表明 IL-24 是 AD 发病和进展的关键因素，也是引人注目的治疗靶点。