Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, 2 D02 YN77 Dublin, Ireland.
Cells. 2019 Jun 5;8(6):543. doi: 10.3390/cells8060543.
Multiple Sclerosis (MS) is a chronic demyelinating autoimmune disease primarily affecting young adults. Despite an unclear causal factor, symptoms and pathology arise from the infiltration of peripheral immune cells across the blood brain barrier. Accounting for the largest fraction of this infiltrate, macrophages are functionally heterogeneous innate immune cells capable of adopting either a pro or an anti-inflammatory phenotype, a phenomenon dependent upon cytokine milieu in the CNS. This functional plasticity is of key relevance in MS, where the pro-inflammatory state dominates the early stage, instructing demyelination and axonal loss while the later anti-inflammatory state holds a key role in promoting tissue repair and regeneration in later remission. This review highlights a potential therapeutic benefit of modulating macrophage polarisation to harness the anti-inflammatory and reparative state in MS. Here, we outline the role of macrophages in MS and look at the role of current FDA approved therapeutics in macrophage polarisation. Moreover, we explore the potential of particulate carriers as a novel strategy to manipulate polarisation states in macrophages, whilst examining how optimising macrophage uptake via nanoparticle size and functionalisation could offer a novel therapeutic approach for MS.
多发性硬化症(MS)是一种慢性脱髓鞘自身免疫性疾病,主要影响年轻人。尽管病因尚不明确,但症状和病理学源于外周免疫细胞穿过血脑屏障的浸润。在这种浸润中,巨噬细胞占最大比例,是具有功能异质性的固有免疫细胞,能够表现出促炎或抗炎表型,这种现象取决于中枢神经系统中的细胞因子环境。这种功能可塑性在 MS 中非常重要,其中促炎状态主导早期阶段,指导脱髓鞘和轴突丢失,而后期的抗炎状态在促进后期缓解中的组织修复和再生中起着关键作用。这篇综述强调了调节巨噬细胞极化以利用 MS 中抗炎和修复状态的潜在治疗益处。在这里,我们概述了巨噬细胞在 MS 中的作用,并研究了当前 FDA 批准的治疗药物在巨噬细胞极化中的作用。此外,我们探讨了颗粒载体作为一种新型策略来操纵巨噬细胞极化状态的潜力,同时研究了通过纳米颗粒大小和功能化来优化巨噬细胞摄取是否为 MS 提供了一种新的治疗方法。