Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Environment Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
Front Immunol. 2021 Aug 20;12:667705. doi: 10.3389/fimmu.2021.667705. eCollection 2021.
Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS). Besides the vital role of T cells, other immune cells, including B cells, innate immune cells, and macrophages (MФs), also play a critical role in MS pathogenesis. Tissue-resident MФs in the brain's parenchyma, known as microglia and monocyte-derived MФs, enter into the CNS following alterations in CNS homeostasis that induce inflammatory responses in MS. Although the neuroprotective and anti-inflammatory actions of monocyte-derived MФs and resident MФs are required to maintain CNS tolerance, they can release inflammatory cytokines and reactivate primed T cells during neuroinflammation. In the CNS of MS patients, elevated myeloid cells and activated MФs have been found and associated with demyelination and axonal loss. Thus, according to the role of MФs in neuroinflammation, they have attracted attention as a therapeutic target. Also, due to their different origin, location, and turnover, other strategies may require to target the various myeloid cell populations. Here we review the role of distinct subsets of MФs in the pathogenesis of MS and different therapeutic agents that target these cells.
多发性硬化症（MS）是一种中枢神经系统（CNS）脱髓鞘炎症性疾病。除 T 细胞外，其他免疫细胞，包括 B 细胞、先天免疫细胞和巨噬细胞（MФ），也在 MS 发病机制中起关键作用。脑实质中的组织驻留巨噬细胞，称为小胶质细胞和单核细胞衍生的巨噬细胞，在 CNS 内稳态改变导致 MS 中炎症反应时进入 CNS。尽管单核细胞衍生的巨噬细胞和驻留巨噬细胞的神经保护和抗炎作用对于维持 CNS 耐受是必需的，但它们可以在神经炎症期间释放炎症细胞因子并重新激活致敏 T 细胞。在 MS 患者的 CNS 中，已发现升高的髓样细胞和激活的巨噬细胞与脱髓鞘和轴突丢失有关。因此，根据巨噬细胞在神经炎症中的作用，它们已作为治疗靶点引起关注。此外，由于它们的不同来源、位置和周转率，可能需要针对不同的髓样细胞群采用其他策略。本文综述了不同巨噬细胞亚群在 MS 发病机制中的作用以及针对这些细胞的不同治疗药物。
