Estrogen receptor β (ERβ) ligands promote remyelination in mouse models of multiple sclerosis. Recent work using experimental autoimmune encephalomyelitis (EAE) has shown that ERβ ligands induce axon remyelination, but impact peripheral inflammation to varying degrees. To identify if ERβ ligands initiate a common immune mechanism in remyelination, central and peripheral immunity and pathology in mice given ERβ ligands at peak EAE were assessed. All ERβ ligands induced differential expression of cytokines and chemokines, but increased levels of CXCL1 in the periphery and in astrocytes. Oligodendrocyte CXCR2 binds CXCL1 and has been implicated in normal myelination. In addition, despite extensive immune cell accumulation in the CNS, all ERβ ligands promoted extensive remyelination in mice at peak EAE. This finding highlights a component of the mechanism by which ERβ ligands mediate remyelination. Hence, interplay between the immune system and central nervous system may be responsible for the remyelinating effects of ERβ ligands. Our findings of potential neuroprotective benefits arising from the presence of CXCL1 could have implications for improved therapies for multiple sclerosis.

雌激素受体β（ERβ）配体在多发性硬化症的小鼠模型中促进髓鞘再生。使用实验性自身免疫性脑脊髓炎（EAE）的最新工作表明，ERβ配体可诱导轴突髓鞘再生，但会不同程度地影响周围炎症。为了鉴定ERβ配体是否在髓鞘再生中启动共同的免疫机制，评估了在EAE峰值时给予ERβ配体的小鼠的中枢和外周免疫及病理。所有ERβ配体均诱导细胞因子和趋化因子的差异表达，但外周和星形胶质细胞中CXCL1的水平升高。少突胶质细胞CXCR2结合CXCL1，并与正常的髓鞘形成有关。此外，尽管中枢神经系统中大量免疫细胞蓄积，但所有ERβ配体均在EAE高峰期促进小鼠的广泛髓鞘再生。这一发现突出了ERβ配体介导髓鞘再生的机制的一个组成部分。因此，免疫系统和中枢神经系统之间的相互作用可能是ERβ配体的髓鞘再生作用的原因。我们对由于存在CXCL1引起的潜在神经保护益处的发现可能对改善多发性硬化症的治疗方法有影响。