Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Department of Immunology, University of Toronto, Toronto, ON, Canada.
Curr Top Behav Neurosci. 2023;62:333-373. doi: 10.1007/7854_2022_324.
Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS) that leads to axonal damage and accumulation of disability. Relapsing-remitting MS (RR-MS) is the most frequent presentation of MS and this form of MS is three times more prevalent in females than in males. This female bias in MS is apparent only after puberty, suggesting a role for sex hormones in this regulation; however, very little is known of the biological mechanisms that underpin the sex difference in MS onset. Experimental autoimmune encephalomyelitis (EAE) is an animal model of RR-MS that presents more severely in females in certain mouse strains and thus has been useful to study sex differences in CNS autoimmunity. Here, we overview the immunopathogenesis of MS and EAE and how immune mechanisms in these diseases differ between a male and female. We further describe how females exhibit more robust myelin-specific T helper (Th) 1 immunity in MS and EAE and how this sex bias in Th cells is conveyed by sex hormone effects on the T cells, antigen presenting cells, regulatory T cells, and innate lymphoid cell populations.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性自身免疫性脱髓鞘疾病，导致轴突损伤和残疾积累。复发缓解型多发性硬化症（RR-MS）是 MS 最常见的表现形式，这种形式的 MS 在女性中的发病率比男性高三倍。这种 MS 的女性偏好在青春期后才明显，表明性激素在这种调节中起作用；然而，对于支持 MS 发病中性别差异的生物学机制知之甚少。实验性自身免疫性脑脊髓炎（EAE）是 RR-MS 的动物模型，在某些小鼠品系中女性表现更为严重，因此对于研究中枢神经系统自身免疫中的性别差异很有用。在这里，我们概述了 MS 和 EAE 的免疫发病机制，以及这些疾病中男性和女性之间的免疫机制有何不同。我们进一步描述了女性在 MS 和 EAE 中表现出更强的髓鞘特异性辅助性 T 细胞（Th）1 免疫，以及性激素如何通过对 T 细胞、抗原呈递细胞、调节性 T 细胞和固有淋巴细胞群的影响来传递 Th 细胞的这种性别偏见。
