Abstract：
Regulatory T cells (Tregs) are a specialized subset of CD4+ T cells essential for the maintenance of immune homeostasis and prevention of autoimmunity. Treg lineage and functions are programmed by the X-chromosome encoded transcription factor Forkhead box P3 (FOXP3). In humans, multiple FOXP3 isoforms are generated through alternative splicing. A full-length isoform containing all coding exons (FOXP3-FL) and a version lacking the second exon (FOXP3-ΔE2) are the predominant FOXP3 isoforms. Additionally, there are two minor isoforms lacking either exon 7 (FOXP3-ΔE7) and both exons 2 and 7 (FOXP3-ΔE2ΔE7). Although healthy humans express approximately equal levels of the FOXP3-FL and FOXP3-ΔE2 isoforms, sole expression of FOXP3-ΔE2 results in development of a systemic autoimmune disease that resembles immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. These clinical observations strongly suggest functional defects in suppression by Tregs programmed by the FOXP3-ΔE2 isoform. Work from the past two decades has provided phenotypic and functional evidence of differences between Tregs programmed by the FOXP3-FL, FOXP3-ΔE2, and FOXP3-ΔE7 isoforms. In this review, we discuss the discovery of the FOXP3 isoforms, differences in the phenotype and function of Tregs programmed by different FOXP3 isoforms, and the role that these isoforms are known to play in autoimmunity.
摘要：
调节性T细胞(Tregs)是对维持免疫稳态和预防自身免疫至关重要的CD4+T细胞的专门子集。Treg谱系和功能由X染色体编码的转录因子Forkhead盒P3(FOXP3)编程。在人类中,通过可变剪接产生多个FOXP3同工型。包含所有编码外显子的全长同种型(FOXP3-FL)和缺少第二外显子的版本(FOXP3-ΔE2)是主要的FOXP3同种型。此外,有两个次要的同工型缺乏外显子7（FOXP3-ΔE7）和外显子2和7（FOXP3-ΔE2ΔE7）。尽管健康人表达大约相等水平的FOXP3-FL和FOXP3-ΔE2亚型,FOXP3-ΔE2的单独表达导致类似于免疫失调的全身性自身免疫性疾病的发展。多内分泌病,肠病,X连锁（IPEX）综合征。这些临床观察结果强烈表明由FOXP3-ΔE2同种型编程的Treg抑制中的功能缺陷。过去二十年的工作提供了FOXP3-FL编程的Tregs之间差异的表型和功能证据，FOXP3-ΔE2和FOXP3-ΔE7同种型。在这次审查中,我们讨论FOXP3亚型的发现，不同FOXP3亚型编程的Treg的表型和功能差异，以及已知这些同工型在自身免疫中的作用。
