Targeting Th17 Cells with Small Molecules and Small Interference RNA.
Targeting Th17 Cells with Small Molecules and Small Interference RNA.
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DOI：
10.1155/2015/290657
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发表时间：
2015
影响因子：
4.6
通讯作者：
Chu CQ
中科院分区：
文献类型：
--
作者：
Lin H;Song P;Zhao Y;Xue LJ;Liu Y;Chu CQ
辅助性T细胞17（Th 17）通过产生促炎细胞因子白细胞介素-（IL-）17、IL-17 F和IL-22在炎性和自身免疫性疾病中发挥核心作用。抗IL-17单克隆抗体在银屑病中显示出有效的疗效，但在类风湿性关节炎（RA）和克罗恩病中效果较差。靶向Th 17细胞的替代药物可能比阻断单一效应细胞因子的抗体更好地抑制Th 17细胞的发育和功能。视黄酸相关孤儿受体γ t（RORγt）作为Th 17细胞分化的主要转录因子，已成为治疗Th 17介导的自身免疫性疾病的重要药物靶点。近年来，随着化学筛选技术和核酸工程技术的发展，以RORγt为靶点的两类新的治疗药物成为可能。化学筛选技术从小分子文库中鉴定出几种RORγt的小分子特异性抑制剂。通过指数富集的配体系统进化（SELEX）技术使得能够从随机序列寡核苷酸文库中分离靶特异性适体。本文综述了以RORγt为靶点的小分子抑制Th 17细胞的研究进展和治疗潜力，以及适体介导的CD 4 + T细胞特异性小干扰RNA（siRNA）对RORγt基因表达的抑制作用。
T helper 17 (Th17) cells play a central role in inflammatory and autoimmune diseases via the production of proinflammatory cytokines interleukin- (IL-) 17, IL-17F, and IL-22. Anti-IL-17 monoclonal antibodies show potent efficacy in psoriasis but poor effect in rheumatoid arthritis (RA) and Crohn's disease. Alternative agents targeting Th17 cells may be a better way to inhibit the development and function of Th17 cells than antibodies of blocking a single effector cytokine. Retinoic acid-related orphan receptor gamma t (RORγt) which acts as the master transcription factor of Th17 differentiation has been an attractive pharmacologic target for the treatment of Th17-mediated autoimmune disease. Recent progress in technology of chemical screen and engineering nucleic acid enable two new classes of therapeutics targeting RORγt. Chemical screen technology identified several small molecule specific inhibitors of RORγt from a small molecule library. Systematic evolution of ligands by exponential enrichment (SELEX) technology enabled target specific aptamers to be isolated from a random sequence oligonucleotide library. In this review, we highlight the development and therapeutic potential of small molecules inhibiting Th17 cells by targeting RORγt and aptamer mediated CD4+ T cell specific delivery of small interference RNA against RORγt gene expression to inhibit pathogenic effector functions of Th17 lineage.