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《工程(英文)》 >> 2019年 第5卷 第1期 doi: 10.1016/j.eng.2019.01.001

作为免疫疗法靶点的FOXP3及其辅因子

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-4238, USA

收稿日期: 2018-07-31 修回日期: 2018-12-11 录用日期: 2019-01-05 发布日期: 2019-01-11

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摘要

叉头框蛋白P3(FOXP3)是调节性T细胞(Tregs)的一个主要调节因子,调节性T细胞是能抑制抗原特异性免疫反应的T 细胞亚群,在增强宿主耐受性和维持免疫平衡方面发挥着重要作用。众所周知,FOXP3 与多种蛋白质形成复合物,并能通过乙酰化、磷酸化、泛素化和甲基化等各种翻译后修饰(PTM)进行调节。因此,翻译后修饰可改变FOXP3 的稳定性及其调节基因表达的能力,并最终影响调节性T细胞活性。虽然FOXP3 自身并非理想的药物靶点,但脱乙酰酶、乙酰转移酶、激酶和其他可调节FOXP3 的翻译后修饰的酶均为调控FOXP3 和调节性T细胞活性的潜在靶点。但FOXP3 并非这些酶的唯一底物;因此,当使用相关抑制剂时,必须考虑是否存在有害的“FOXP3脱靶”副作用。在本文中,我们总结了有关FOXP3 辅助因子和蛋白质翻译后修饰的最新研究进展,以及它们在自体免疫和癌症免疫中的潜在临床应用。

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