Multiple sclerosis (MS) is a neurodegenerative autoimmune disease characterized by the destruction of the myelin sheath of the neuronal axon in the central nervous system. Many risk factors, including environmental, epigenetic, genetic, and lifestyle factors, are responsible for the development of MS. It has long been thought that only adaptive immune cells, especially autoreactive T cells, are responsible for the pathophysiology; however, recent evidence has indicated that innate immune cells are also highly involved in disease initiation and progression. Here, we compile the available data regarding the role immune cells play in MS, drawn from both human and animal research. While T and B lymphocytes, chiefly enhance MS pathology, regulatory T cells (Tregs) may serve a more protective role, as can B cells, depending on context and location. Cells chiefly involved in innate immunity, including macrophages, microglia, astrocytes, dendritic cells, natural killer (NK) cells, eosinophils, and mast cells, play varied roles. In addition, there is evidence regarding the involvement of innate-like immune cells, such as γδ T cells, NKT cells, MAIT cells, and innate-like B cells as crucial contributors to MS pathophysiology. It is unclear which of these cell subsets are involved in the onset or progression of disease or in protective mechanisms due to their plastic nature, which can change their properties and functions depending on microenvironmental exposure and the response of neural networks in damage control. This highlights the need for a multipronged approach, combining stringently designed clinical data with carefully controlled in vitro and in vivo research findings, to identify the underlying mechanisms so that more effective therapeutics can be developed.

中文翻译：

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免疫细胞反应的可塑性使剖析多发性硬化症的潜在病理学变得复杂

多发性硬化症（MS）是一种神经退行性自身免疫性疾病，其特征是中枢神经系统神经元轴突髓鞘的破坏。许多危险因素，包括环境、表观遗传、遗传和生活方式因素，都会导致多发性硬化症的发生。长期以来，人们一直认为只有适应性免疫细胞，尤其是自身反应性 T 细胞，才对病理生理学负责。然而，最近的证据表明，先天免疫细胞也高度参与疾病的发生和进展。在这里，我们汇总了来自人类和动物研究的有关免疫细胞在多发性硬化症中所起作用的可用数据。虽然 T 和 B 淋巴细胞主要增强 MS 病理学，但调节性 T 细胞 (Treg) 可能发挥更大的保护作用，B 细胞也可以，具体取决于环境和位置。主要参与先天免疫的细胞，包括巨噬细胞、小胶质细胞、星形胶质细胞、树突状细胞、自然杀伤（NK）细胞、嗜酸性粒细胞和肥大细胞，发挥着不同的作用。此外，有证据表明先天性免疫细胞（例如γδ T 细胞、NKT 细胞、MAIT 细胞和先天性 B 细胞）是 MS 病理生理学的重要贡献者。目前尚不清楚这些细胞亚群中的哪些细胞亚群由于其可塑性而参与疾病的发生或进展或保护机制，这可以根据微环境暴露和神经网络在损伤控制中的反应来改变它们的特性和功能。这凸显了需要采取多管齐下的方法，将严格设计的临床数据与精心控制的体外和体内研究结果相结合，以确定潜在的机制，以便开发出更有效的治疗方法。