Qian Xinmin, Tong Meiyi, Zhang Tianqing, Li Qingqing, Hua Meng, Zhou Nan, Zeng Wenwen
Institute for Immunology and School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University, Beijing 100084, China.
Eight-year Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100084, China.
Protein Cell. 2025 Mar 8;16(3):188-210. doi: 10.1093/procel/pwae030.
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.
特应性皮炎（AD）是一种常见的炎症性皮肤病，患者会反复出现湿疹样皮损并伴有剧烈瘙痒。金黄色葡萄球菌（金葡菌）的定植与疾病严重程度相关，但其在AD发病中的作用仍不明确。通过单细胞RNA测序，我们发现角质形成细胞在暴露于耐甲氧西林金葡菌（MRSA）时会激活一种以诱导Il24为特征的独特免疫反应。使用动物模型的进一步实验表明，给予重组IL-24蛋白会加重AD样病理变化。角质形成细胞中Il24或其受体Il20rb的基因敲除减轻了过敏性炎症和特应性进程。从机制上讲，IL-24通过其在角质形成细胞上的异二聚体受体发挥作用，增加了IL-33的产生，进而加重了2型免疫反应和AD样皮肤状况。总体而言，这些发现确立了IL-24是AD发病和进展的关键因素以及一个有吸引力的治疗靶点。
