摘要
X-连锁多内分泌腺病、肠病伴免疫失调综合征是一种由于叉头状Forkhead box P3 (FOXP3)基因在编码过程中发生突变而引发的罕见的自身免疫性疾病。Forkhead box P3是一种转录因子,它是胸腺衍生的调节性T 细胞 (Treg细胞)发挥正常功能的基础。Treg细胞的功能异常会引起多个器官的自身免疫异常,如果不能及时进行造血干细胞移植治疗(HSCT),最终会导致婴儿过早死亡。为了取得比异体造血干细胞移植疗法更好的最终治愈效果,IPEX综合征新的基因治疗策略正在被开发。在此,我们介绍了正处于开发过程中的替代造血干细胞移植疗法的其他治疗方法。我们介绍了效应T细胞可以在调节性T细胞中被转化。这种转化是在分化的T淋巴细胞中通过慢病毒载体介导的 FOXP3基因转移发生的。尽管FOXP3基因突变主要影响高度特异性T细胞亚群,为了能使这种疾病得到长期缓解,仍需要能操控干细胞。因此,我们认为,应该有一种更全面的战略着眼于修正FOXP3突变的干细胞。在这里,这两种治疗策略的潜力和障碍将被着重探讨。
关键词: 自身免疫性疾病、细胞疗法、Forkhead box P3基因、基因修正、X-连锁多内分泌腺病、肠病伴免疫失调综合征 慢病毒载体、调节性T细胞
Current Gene Therapy
Title:Gene/Cell Therapy Approaches for Immune Dysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome
Volume: 14 Issue: 6
Author(s): Laura Passerini, Francesca R. Santoni de Sio, Matthew H. Porteus and Rosa Bacchetta
Affiliation:
关键词: 自身免疫性疾病、细胞疗法、Forkhead box P3基因、基因修正、X-连锁多内分泌腺病、肠病伴免疫失调综合征 慢病毒载体、调节性T细胞
摘要: Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare autoimmune disease due to mutations in the gene encoding for Forkhead box P3 (FOXP3), a transcription factor fundamental for the function of thymus-derived (t) regulatory T (Treg) cells. The dysfunction of Treg cells results in the development of devastating autoimmune manifestations affecting multiple organs, eventually leading to premature death in infants, if not promptly treated by hematopoietic stem cell transplantation (HSCT). Novel gene therapy strategies can be developed for IPEX syndrome as more definitive cure than allogeneic HSCT. Here we describe the therapeutic approaches, alternative to HSCT, currently under development. We described that effector T cells can be converted in regulatory T cells by LVmediated FOXP3-gene transfer in differentiated T lymphocytes. Despite FOXP3 mutations mainly affect a highly specific T cell subset, manipulation of stem cells could be required for long-term remission of the disease. Therefore, we believe that a more comprehensive strategy should aim at correcting FOXP3-mutated stem cells. Potentials and hurdles of both strategies will be highlighted here.
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Passerini Laura, Sio R. Santoni de Francesca, Porteus H. Matthew and Bacchetta Rosa, Gene/Cell Therapy Approaches for Immune Dysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome, Current Gene Therapy 2014; 14 (6) . https://dx.doi.org/10.2174/1566523214666141001123828
DOI https://dx.doi.org/10.2174/1566523214666141001123828 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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