Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
J Genet Genomics. 2020 Jan 20;47(1):17-26. doi: 10.1016/j.jgg.2019.11.011. Epub 2020 Jan 24.
Regulatory T (Treg) cells, a subtype of immunosuppressive CD4 T cells, are vital for maintaining immune homeostasis in healthy people. Forkhead box protein P3 (FOXP3), a member of the forkhead-winged-helix family, is the pivotal transcriptional factor of Treg cells. The expression, post-translational modifications, and protein complex of FOXP3 present a great impact on the functional stability and immune plasticity of Treg cells in vivo. In particular, the mutation of FOXP3 can result in immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, which is a rare genetic disease mostly diagnosed in early childhood and can soon be fatal. IPEX syndrome is related to several manifestations, including dermatitis, enteropathy, type 1 diabetes, thyroiditis, and so on. Here, we summarize some recent findings on FOXP3 regulation and Treg cell function. We also review the current knowledge about the underlying mechanism of FOXP3 mutant-induced IPEX syndrome and some latest clinical prospects. At last, this review offers a novel insight into the role played by the FOXP3 complex in potential therapeutic applications in IPEX syndrome.
调节性 T（Treg）细胞是一种具有免疫抑制作用的 CD4 T 细胞亚群，对于维持健康人群的免疫稳态至关重要。叉头框蛋白 P3（FOXP3）是叉头翼螺旋转录因子家族的成员，是 Treg 细胞的关键转录因子。FOXP3 的表达、翻译后修饰和蛋白复合物对 Treg 细胞在体内的功能稳定性和免疫可塑性有很大影响。特别是 FOXP3 的突变可导致免疫失调、多内分泌腺病、肠病、X 连锁（IPEX）综合征，这是一种罕见的遗传性疾病，主要在儿童早期诊断，很快就会致命。IPEX 综合征与多种表现有关，包括皮炎、肠炎、1 型糖尿病、甲状腺炎等。在这里，我们总结了一些关于 FOXP3 调节和 Treg 细胞功能的最新发现。我们还回顾了 FOXP3 突变诱导的 IPEX 综合征的潜在机制的现有知识和一些最新的临床前景。最后，本综述为 FOXP3 复合物在 IPEX 综合征潜在治疗应用中的作用提供了新的见解。
