Attenuation of wnt/β-catenin signaling in patients with stevens-johnson syndrome and toxic epidermal necrolysis

Chun Bing Chen, Wan Chun Chang, Ming Ying Wu, Tzu Yang Kao, Ying Wen Wang, Chuang Wei Wang, Chi Ju Chen, Wen Hung Chung, Shih Chi Su*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) are rare but life-threatening severe cutaneous adverse reactions. Current studies have suggested that the pathobiology of drug-mediated SJS/TEN involves a dysregulation of cellular immunity with overwhelming activation of cytotoxic T lymphocytes. The canonical Wnt signaling pathway plays important roles in T cell development and activation, which may provide potential avenues for alleviating dysregulated immunity in SJS/TEN. In this study, we aimed to assess the implication of Wnt signaling in drug-reactive T cells in SJS/TEN. We showed downregulation of Wnt signaling components, including T cell factor 1 (TCF-1)/lymphoid enhancer binding factor 1 (LEF-1) transcription factors, in SJS/TEN patients, suggesting that canonical Wnt signaling is regulated during cytotoxic T cell responses in SJS/TEN. Further analyses demonstrated that engagement of the T cell receptor by antigen encounter and treatment of a prognostic marker of SJS/TEN, IL-15, in vitro led to the downregulation of LEF-1 and TCF-1 expression in CD8+ T cells. Enhancement of Wnt signaling by adding the Wnt activators attenuated ex vivo activation of drug-specific T cells from SJS/TEN patients, indicating a functional involvement of Wnt signaling in the pathomechanism of SJS/TEN. These findings provide additional insight into the immunopathogenesis and therapeutic intervention of this devastating condition.

原文英語
頁(從 - 到)353-364
頁數12
期刊International Journal of Biological Sciences
16
發行號2
DOIs
出版狀態已出版 - 2019

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