國家衛生研究院 NHRI:Item 3990099045/15739
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    题名: Dominant dystrophic epidermolysis bullosa is associated with glycolytically active GATA3+ T helper 2 cells which may contribute to pruritus in lesional skin
    作者: Aala, WJF;Hou, PC;Hong, YK;Lin, YC;Lee, YR;Tu, WT;Papanikolaou, M;Benzian-Olsson, N;Onoufriadis, A;H, ICH;Hwang, DY;Cheng, SM;Lu, K;Chen, PC;McGrath, JA;Hsu, CK
    贡献者: National Institute of Cancer Research
    摘要: BACKGROUND: Dominant dystrophic epidermolysis bullosa (DDEB) is characterized by trauma-induced blisters and, in some individuals, intense pruritus. Precisely what causes itch in DDEB and optimal ways to reduce it have not been fully determined. OBJECTIVE: To characterize DDEB skin transcriptomes to identify therapeutic targets to reduce pruritus in patients. METHODS: We evaluated affected and unaffected skin biopsy samples from 6 DDEB subjects (all with the very itchy pruriginosa subtype), and 4 healthy individuals using bulk RNA-seq. Single-cell transcriptomes of affected (n=2) and unaffected (n=1) DDEB and healthy skin (n=2) were obtained. Dupilumab treatment was provided for three patients. RESULTS: The skin bulk transcriptome showed significant enrichment of Th1/2 and Th17 pathways in affected DDEB skin compared with non-lesional DDEB and healthy skin. Single-cell transcriptomics showed an association of glycolytically active GATA3+ Th2 cells in affected DDEB skin. Treatment with dupilumab in three people with DDEB led to significantly reduced VAS itch scores after 12 weeks (mean VAS=3.83) compared to pre-treatment (mean VAS=7.83). Bulk RNA-seq and qPCR showed that healthy skin and dupilumab-treated epidermolysis bullosa (EB) pruriginosa skin show very similar transcriptomic profiles, and reduced Th1/2 and Th17 pathway enrichment. CONCLUSIONS: Single-cell RNA-seq helps define an enhanced DDEB-associated Th2 profile and rationalizes drug repurposing of anti-Th2 drugs in treating DDEB pruritus.
    日期: 2024-08
    關聯: British Journal of Dermatology. 2024 Aug;191(2):252-260.
    Link to: http://dx.doi.org/10.1093/bjd/ljae110
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0007-0963&DestApp=IC2JCR
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85199046541
    显示于类别:[黃道揚] 期刊論文

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