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作者

Lele Sun Pengcheng Huai Zhenzhen Wang Qing Zhao Yingjie Lin Tingting Liu Xiaotong Xue Suiting Ao Jiabao You Yonghu Sun Zihao Mi Joshua Gardner Paul J.Thomson Dean J.Naisbitt Xiaoli Meng Jianjun Liu Hong Liu Furen Zhang

作者单位

Dermatology Hospital of Shandong First Medical University

刊名

信号转导与靶向治疗(英文)

年份

2025

卷号

第7期

页码

3906-3919

关键词

NK cells Drug hypersensitivity CD T cells TSC D severe cutaneous adverse drug reactions scars HLA risk variants dapsone hypersensitivity syndrome dhs Dapsone hypersensitivity syndrome

分类号

R392

摘要

Severe cutaneous adverse drug reactionsare life-threatening diseases,which are associated with human leukocyte antigenrisk variants.However,the low positive predictive values of HLA variants suggest additional factors influence disease susceptibility.Using dapsone hypersensitivity syndromeas a paradigm for SCARs,we show that the DHS patients harbor a sex-related global reduction in blood NK cells,contributing to the higher incidence of reactions in females.Single-cell RNA sequencing revealed a d...更多

Severe cutaneous adverse drug reactionsare life-threatening diseases,which are associated with human leukocyte antigenrisk variants.However,the low positive predictive values of HLA variants suggest additional factors influence disease susceptibility.Using dapsone hypersensitivity syndromeas a paradigm for SCARs,we show that the DHS patients harbor a sex-related global reduction in blood NK cells,contributing to the higher incidence of reactions in females.Single-cell RNA sequencing revealed a decrease in the immunoregulatory CD56low XCL1/2low NK cell subset and an expansion of CD56high XCL1/2high NK cell subsets with an effector phenotype in DHS patients compared to dapsone-tolerant individuals.Functionally,interleukin-15 superagonist-induced activation of NK cells exacerbated SCARs-like symptoms in a murine model.Mechanistically,TSC22 domain family member 3deficiency enhanced NK cell effector function,shifting the immune response from CD4+T cell to CD8+T cell function.These results demonstrate that TSC22D3-regulated NK cells play a critical role in predisposing to drug hypersensitivity reactions,bridging innate and adaptive immune dysregulation in SCARs pathogenesis.Our study highlights the importance of NK cell heterogeneity and TSC22D3 in immune-mediated hypersensitivity disorders,offering potential therapeutic targets for SCARs and related conditions.收起

基金

国家自然科学基金

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