Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PP, UK.
Cells. 2024 May 8;13(10):797. doi: 10.3390/cells13100797.
Multiple sclerosis is an autoinflammatory condition that results in damage to myelinated neurons in affected patients. While disease-modifying treatments have been successful in slowing the progression of relapsing-remitting disease, most patients still progress to secondary progressive disease that is largely unresponsive to disease-modifying treatments. Similarly, there is currently no effective treatment for patients with primary progressive MS. Innate and adaptive immune cells in the CNS play a critical role in initiating an autoimmune attack and in maintaining the chronic inflammation that drives disease progression. In this review, we will focus on recent insights into the role of T cells with regulatory function in suppressing the progression of MS, and, more importantly, in promoting the remyelination and repair of MS lesions in the CNS. We will discuss the exciting potential to genetically reprogram regulatory T cells to achieve immune suppression and enhance repair locally at sites of tissue damage, while retaining a fully competent immune system outside the CNS. In the future, reprogramed regulatory T cells with defined specificity and function may provide life medicines that can persist in patients and achieve lasting disease suppression after one cycle of treatment.
多发性硬化症是一种自身炎症性疾病,导致受影响患者髓鞘神经元受损。虽然疾病修正治疗已成功减缓复发缓解型疾病的进展,但大多数患者仍进展为继发进展型疾病,对疾病修正治疗反应不佳。同样,目前尚无针对原发性进展型多发性硬化症患者的有效治疗方法。中枢神经系统中的固有和适应性免疫细胞在引发自身免疫攻击以及维持驱动疾病进展的慢性炎症方面发挥着关键作用。在这篇综述中,我们将重点介绍最近关于具有调节功能的 T 细胞在抑制多发性硬化症进展,以及更重要的是,在促进中枢神经系统多发性硬化症病变的髓鞘再生和修复方面的作用的新见解。我们将讨论通过基因重编程调节性 T 细胞以实现免疫抑制并在组织损伤部位局部增强修复的令人兴奋的潜力,同时在中枢神经系统外保留完全有效的免疫系统。在未来,具有明确特异性和功能的重编程调节性 T 细胞可能提供可以在患者体内持续存在并在一个治疗周期后实现持久疾病抑制的生命药物。