{"title":"IL-24 通过驱动 MRSA 诱导的过敏反应,促进特应性皮炎样炎症。","authors":"Xinmin Qian, Meiyi Tong, Tianqing Zhang, Qingqing Li, Meng Hua, Nan Zhou, Wenwen Zeng","doi":"10.1093/procel/pwae030","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":null,"pages":null},"PeriodicalIF":13.6000,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"IL-24 promotes atopic dermatitis-like inflammation through driving MRSA-induced allergic responses.\",\"authors\":\"Xinmin Qian, Meiyi Tong, Tianqing Zhang, Qingqing Li, Meng Hua, Nan Zhou, Wenwen Zeng\",\"doi\":\"10.1093/procel/pwae030\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":20790,\"journal\":{\"name\":\"Protein & Cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":13.6000,\"publicationDate\":\"2024-05-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Protein & Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1093/procel/pwae030\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Protein & Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/procel/pwae030","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
特应性皮炎(AD)是一种常见的炎症性皮肤病,患者会出现反复发作的湿疹和剧烈瘙痒。金黄色葡萄球菌(S. aureus)的定植与疾病的严重程度相关,但它在特应性皮炎发展过程中的作用仍然难以捉摸。通过单细胞 RNA 测序,我们发现角朊细胞在暴露于耐甲氧西林金黄色葡萄球菌(MRSA)时会激活以诱导 Il24 为特征的独特免疫反应。使用动物模型进行的进一步实验表明,服用重组IL-24蛋白会加重AD样病理学。对IL-24或角质形成细胞中的受体Il20rb进行基因消减可减轻过敏性炎症和特应性进展。从机理上讲,IL-24通过其在角质形成细胞上的异二聚体受体发挥作用,促进了IL-33的产生,而IL-33的产生反过来又加剧了2型免疫和AD样皮肤病。总之,这些研究结果表明,IL-24 是导致 AD 发病和进展的关键因素,也是一个引人注目的治疗靶点。
IL-24 promotes atopic dermatitis-like inflammation through driving MRSA-induced allergic responses.
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.
期刊介绍:
Protein & Cell is a monthly, peer-reviewed, open-access journal focusing on multidisciplinary aspects of biology and biomedicine, with a primary emphasis on protein and cell research. It publishes original research articles, reviews, and commentaries across various fields including biochemistry, biophysics, cell biology, genetics, immunology, microbiology, molecular biology, neuroscience, oncology, protein science, structural biology, and translational medicine. The journal also features content on research policies, funding trends in China, and serves as a platform for academic exchange among life science researchers.