Forkhead-Box-P3 Gene Transfer in Human CD4(+) T Conventional Cells for the Generation of Stable and Efficient Regulatory T Cells, Suitable for Immune Modulatory Therapy.
Forkhead-Box-P3 Gene Transfer in Human CD4(+) T Conventional Cells for the Generation of Stable and Efficient Regulatory T Cells, Suitable for Immune Modulatory Therapy.
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Forkhead-Box-P3基因在人CD4(+)T常规细胞中的转移用于生成稳定高效的调节性T细胞，适用于免疫调节治疗。
DOI：
10.3389/fimmu.2017.01282
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发表时间：
2017
影响因子：
7.3
通讯作者：
Bacchetta R
中科院分区：
文献类型：
--
作者：
Passerini L;Bacchetta R
控制对自身和同种异体组织/器官的免疫应答的新方法的开发代表了自身免疫性疾病的管理和移植的雄心勃勃的目标。调节性T细胞（Treg）被认为是在生理和病理条件下维持外周耐受性的关键参与者，并且已经设计了用于恢复T细胞介导的病症中的耐受性的基于Treg的细胞疗法。然而，几个障碍，包括TdR数量不足，其稳定性和抗原特异性，对TdR的临床适用性提出了挑战。在过去的十年中，工程化T细胞的能力已经被证明是一种强大的工具，可以重新定向不同细胞类型的特异性和功能，用于特定的治疗目的。通过使用慢病毒介导的基因转移的胸腺衍生的Treg转录因子叉头盒-P3（FOXP 3）在传统的CD 4 + T细胞，我们转换成Treg样细胞的效应T细胞，赋予有效的体外和体内抑制活性。所得的CD 4FOXP 3 T细胞群体显示稳定的表型和抑制功能。我们表明，这种策略恢复了携带FOXP 3突变的患者[免疫失调，多内分泌病，肠病，X连锁（IPEX）]的T淋巴细胞中的Treg功能，其中CD 4FOXP 3 T细胞可用作控制自身免疫的治疗剂。在这里，我们将讨论使用CD 4FOXP 3 T细胞在炎症性疾病中的体内应用的潜在优势，其中组织炎症可能破坏天然T细胞的功能。这些发现为工程调节性T细胞不仅在IPEX综合征中，而且在不同来源的自身免疫性疾病以及干细胞和器官移植背景下的使用铺平了道路。
The development of novel approaches to control immune responses to self- and allogenic tissues/organs represents an ambitious goal for the management of autoimmune diseases and in transplantation. Regulatory T cells (Tregs) are recognized as key players in the maintenance of peripheral tolerance in physiological and pathological conditions, and Treg-based cell therapies to restore tolerance in T cell-mediated disorders have been designed. However, several hurdles, including insufficient number of Tregs, their stability, and their antigen specificity, have challenged Tregs clinical applicability. In the past decade, the ability to engineer T cells has proven a powerful tool to redirect specificity and function of different cell types for specific therapeutic purposes. By using lentivirus-mediated gene transfer of the thymic-derived Treg transcription factor forkhead-box-P3 (FOXP3) in conventional CD4+ T cells, we converted effector T cells into Treg-like cells, endowed with potent in vitro and in vivo suppressive activity. The resulting CD4FOXP3 T-cell population displays stable phenotype and suppressive function. We showed that this strategy restores Treg function in T lymphocytes from patients carrying mutations in FOXP3 [immune-dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)], in whom CD4FOXP3 T cell could be used as therapeutics to control autoimmunity. Here, we will discuss the potential advantages of using CD4FOXP3 T cells for in vivo application in inflammatory diseases, where tissue inflammation may undermine the function of natural Tregs. These findings pave the way for the use of engineered Tregs not only in IPEX syndrome but also in autoimmune disorders of different origin and in the context of stem cell and organ transplantation.
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影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
影响因子：
4.4
作者：
Baecher-Allan, Clare;Wolf, Elizabeth;Haller, David A.
通讯作者：
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影响因子：
2.7
作者：
Bonini, C;Ciceri, F;Bordignon, C
通讯作者：
Bordignon, C
影响因子：
20.3
作者：
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通讯作者：
Montini, Eugenio
影响因子：
20.3
作者：
Ciceri, Fabio;Bonini, Chiara;Bordignon, Claudio
通讯作者：
Bordignon, Claudio