IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
Genes (Basel). 2022 Jul 24;13(8):1319. doi: 10.3390/genes13081319.
Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder of the central nervous system that presents heterogeneous clinical manifestations and course. It has been shown that different immune checkpoints, including Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), can be involved in the pathogenesis of MS. CTLA-4 is a critical regulator of T-cell homeostasis and self-tolerance and represents a key inhibitor of autoimmunity. In this scopingreview, we resume the current preclinical and clinical studies investigating the role of CTLA-4 in MS with different approaches. While some of these studies assessed the expression levels of CTLA-4 on T cells by comparing MS patients with healthy controls, others focused on the evaluation of the effects of common MS therapies on CTLA-4 modulation or on the study of the CTLA-4 blockade or deficiency in experimental autoimmune encephalomyelitis models. Moreover, other studies in this field aimed to discover if the gene might be involved in the predisposition to MS, whereas others evaluated the effects of treatment with CTLA4-Ig in MS. Although these results are of great interest, they are often conflicting. Therefore, further studies are needed to reveal the exact mechanisms underlying the action of a crucial immune checkpoint such as CTLA-4 in MS to identify novel immunotherapeutic strategies for MS patients.
多发性硬化症 (MS) 是一种中枢神经系统的自身免疫性神经退行性疾病，具有异质性的临床表现和病程。已经表明，包括细胞毒性 T 淋巴细胞抗原 4（CTLA-4）在内的不同免疫检查点可能参与 MS 的发病机制。CTLA-4 是 T 细胞稳态和自身耐受的关键调节剂，代表着自身免疫的关键抑制剂。在这项范围综述中，我们总结了目前使用不同方法研究 CTLA-4 在 MS 中的作用的临床前和临床研究。虽然其中一些研究通过比较 MS 患者和健康对照来评估 CTLA-4 在 T 细胞上的表达水平，但其他研究则侧重于评估常见 MS 治疗方法对 CTLA-4 调节的影响，或研究 CTLA-4 阻断或缺乏在实验性自身免疫性脑脊髓炎模型中的作用。此外，该领域的其他研究旨在确定该基因是否可能与 MS 的易感性有关，而其他研究则评估了 CTLA4-Ig 在 MS 中的治疗效果。尽管这些结果非常有趣，但它们往往存在冲突。因此，需要进一步的研究来揭示 CTLA-4 等关键免疫检查点在 MS 中作用的确切机制，以确定针对 MS 患者的新型免疫治疗策略。
