Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination of the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) shows promising benefits for relapsing–remitting MS in open-label clinical studies, but the cellular mechanisms underlying its therapeutic effects remain unclear. Using single-nucleus RNA sequencing, we identify a reactive myeloid cell state in chronic experimental autoimmune encephalitis (EAE) associated with neuroprotection and immune suppression. HCT in EAE mice results in an increase of the neuroprotective myeloid state, improvement of neurological deficits, reduced number of demyelinated lesions, decreased number of effector T cells and amelioration of reactive astrogliosis. Enhancing myeloid cell incorporation after a modified HCT further improved these neuroprotective effects. These data suggest that myeloid cell manipulation or replacement may be an effective therapeutic strategy for chronic inflammatory conditions of the CNS.

多发性硬化症（MS）是一种以中枢神经系统（CNS）脱髓鞘为特征的自身免疫性疾病。在开放标签临床研究中，自体造血细胞移植（HCT）显示出对复发缓解型多发性硬化症有希望的益处，但其治疗作用背后的细胞机制仍不清楚。利用单核 RNA 测序，我们确定了慢性实验性自身免疫性脑炎 (EAE) 中与神经保护和免疫抑制相关的反应性骨髓细胞状态。 EAE 小鼠的 HCT 导致神经保护性骨髓状态增加、神经功能缺陷改善、脱髓鞘病变数量减少、效应 T 细胞数量减少以及反应性星形胶质细胞增生改善。改良 HCT 后增强骨髓细胞掺入进一步改善了这些神经保护作用。这些数据表明，骨髓细胞操作或替代可能是中枢神经系统慢性炎症的有效治疗策略。