期刊
JOURNAL OF IMMUNOLOGY
卷 204, 期 8, 页码 2053-2063出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1901215
关键词
-
类别
资金
- National Natural Science Foundation of China [81530027]
- Shenzhen Science and Technology Innovation Committee [JCYJ20170413165432016]
- Shandong Provincial Natural Science Foundation [ZR2019MH135]
- Young Taishan Scholarship Project [tsqn201909188]
Autoimmune diseases are a physiological state that immune responses are directed against and damage the body's own tissues. Numerous studies have demonstrated promising therapeutic effects in certain autoimmune diseases by targeting IL-23/IL-17 axis, mostly through using Abs against IL-23 or IL-17A. Pyrrole-imidazole polyamides are nuclease-resistant compounds that inhibit gene expression through binding to the minor groove of DNA. To develop a novel gene-silencing agent that targets IL-23/IL-17 axis, we designed polyamide that specifically binds to the transcription factor c-Rel-binding site located in the promoter of IL-23p19 subunit. Our study showed that this polyamide is capable of entering into nucleus with high efficiency in dendritic cells and macrophage. In addition, it prevented the binding of c-Rel to the promoter of IL-23p19 in vivo and specifically inhibited the expression of IL-23. More importantly, we demonstrated that this polyamide is therapeutically effective using both the imiquimod-induced psoriasis and experimental autoimmune uveitis mouse models. Taken together, these results indicate that pyrrole-imidazole polyamide targeting IL-23p19 could be a novel and feasible therapeutic strategy for patients with autoimmune diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据