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调节性T细胞:葡萄膜炎的治疗机遇

Regulatory T Cells: Therapeutic Opportunities in Uveitis.

作者信息

Lee Andrew YongJae, Foulsham William

机构信息

Department of Ophthalmology, Weill Cornell Medical College, New York, NY, United States.

出版信息

Front Ophthalmol (Lausanne). 2022 May 25;2:901144. doi: 10.3389/fopht.2022.901144. eCollection 2022.

Abstract

Regulatory T cells (Tregs) are critical for the maintenance of immune tolerance and the suppression of excessive inflammation. Many inflammatory autoimmune disorders, including autoimmune uveitis, involve the loss of the suppressive capacities of Tregs. Over the past decade, Tregs' therapeutic potential in uveitis has garnered increasing attention. Specific subsets of Tregs, including TIGIT+ and PD-1+ Tregs, have emerged as potent immunosuppressors that may be particularly well-suited to cell-based therapeutics. Studies have elucidated the interaction between Treg development and the gut microbiome as well as various intracellular signaling pathways. Numerous cell-based therapies and therapeutic molecules have been proposed and investigated using the murine experimental autoimmune uveitis (EAU) model. However, certain challenges remain to be addressed. Studies involving the use of Tregs in human patients with uveitis are lacking, and there are concerns regarding Tregs' production and purification for practical use, their plasticity towards inflammatory phenotypes, immunogenicity, and tumorigenicity. Nevertheless, recent research has brought Tregs closer to yielding viable treatment options for uveitis.

摘要

调节性T细胞(Tregs)对于维持免疫耐受和抑制过度炎症至关重要。许多炎症性自身免疫性疾病,包括自身免疫性葡萄膜炎,都涉及Tregs抑制能力的丧失。在过去十年中,Tregs在葡萄膜炎中的治疗潜力越来越受到关注。特定的Tregs亚群,包括TIGIT+和PD-1+ Tregs,已成为强效免疫抑制剂,可能特别适合基于细胞的治疗。研究已经阐明了Treg发育与肠道微生物群以及各种细胞内信号通路之间的相互作用。使用小鼠实验性自身免疫性葡萄膜炎(EAU)模型已经提出并研究了许多基于细胞的疗法和治疗分子。然而,仍然存在一些挑战需要解决。缺乏涉及在人类葡萄膜炎患者中使用Tregs的研究,并且对于Tregs用于实际应用的生产和纯化、它们向炎症表型的可塑性、免疫原性和致瘤性存在担忧。尽管如此,最近的研究已使Tregs更接近为葡萄膜炎提供可行的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee46/11182269/e18c2a8bfce2/fopht-02-901144-g001.jpg

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