Bidirectional immunoregulation of calcineurin inhibitor tacrolimus on FOXP3 transcription?
Bidirectional immunoregulation of calcineurin inhibitor tacrolimus on FOXP3 transcription?
复制标题
钙调神经磷酸酶抑制剂他克莫司对 FOXP3 转录的双向免疫调节？
DOI：
10.1016/j.mehy.2010.09.011
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发表时间：
2011-02-01
影响因子：
4.7
通讯作者：
Hao, Fei
中科院分区：
文献类型：
--
作者：
Shen, Zhu;Song, Qiuhe;Hao, Fei
调节性 T 细胞 (Treg) 和效应 T 细胞之间的不平衡对于寻常型银屑病的维持很重要。 FOXP3 是 Tregs 发育和功能的主控转录因子，对于转录抑制至关重要。他克莫司可有效治疗寻常型银屑病。数据显示他克莫司对FOXP3具有多重影响，但他克莫司对FOXP3的确切药理机制尚未阐明。我们在此建议他克莫司对 FOXP3 的双向免疫调节。高浓度的他克莫司使 NFAT 与 STAT6 和 NF-kappa B 协同激活 GATA3 转录。相反，低浓度的他克莫司导致细胞核中NFAT水平升高，其直接与FOXP3增强子结合和/或与Smad3协同激活FOXP3转录。需要使用功能丧失和过度表达方法进行进一步研究，以确定参与他克莫司对 FOXP3 双向免疫调节的详细分子。 (C) 2010 Elsevier Ltd. 保留所有权利。
The imbalance between regulatory T cells (Treg) and effector T cells is important for maintaining of psoriasis vulgaris. FOXP3 is a master control transcription factor for the development and function of Tregs and is critical for transcriptional repression. Tacrolimus is effective in treatment of psoriasis vulgaris. Data show that tacrolimus has multiple impacts on FOXP3, but the exact pharmacological mechanism of tacrolimus on FOXP3 have yet to be elucidated. We herein suggest the bidirectional immunoregulation of tacrolimus on FOXP3. High concentration of tacrolimus renders the cooperation of NFAT with STAT6 and NF-kappa B to activate GATA3 transcription. On the contrary, low concentration of tacrolimus results in higher nucleus level of NFAT, which directly binds to FOXP3 enhancer and/or cooperates with Smad3 to activate FOXP3 transcription. Further studies using loss of function and over-expression methods are needed to determine the detailed molecules involved in this bidirectional immunoregulation of tacrolimus on FOXP3. (C) 2010 Elsevier Ltd. All rights reserved.