Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis

被引:3
|
作者
Mader, Marius Marc-Daniel [1 ,2 ,3 ]
Napole, Alan [1 ,2 ,3 ]
Wu, Danwei [1 ,2 ,3 ,4 ,5 ]
Atkins, Micaiah [6 ]
Scavetti, Alexa [1 ,2 ,3 ]
Shibuya, Yohei [1 ,2 ,3 ]
Foltz, Aulden [6 ]
Hahn, Oliver [6 ]
Yoo, Yongjin [1 ,2 ,3 ]
Danziger, Ron [1 ,2 ,3 ]
Tan, Christina [1 ,2 ,3 ]
Wyss-Coray, Tony [6 ]
Steinman, Lawrence [4 ,5 ]
Wernig, Marius [1 ,2 ,3 ]
机构
[1] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
[4] Stanford Univ, Dept Neurol & Neurosci, Div Neuroimmunol, Stanford, CA USA
[5] Stanford Univ, Multiple Sclerosis Ctr, Stanford, CA USA
[6] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA USA
基金
美国国家卫生研究院;
关键词
REMITTING MULTIPLE-SCLEROSIS; TRANSPLANTATION; MICROGLIA; THERAPY; REPERTOIRE; DISEASE;
D O I
10.1038/s41593-024-01609-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. Hematopoietic cell transplantation (HCT) may be a promising therapy for treatment-refractory multiple sclerosis (MS). Mader et al. Describe beneficial effects of autologous HCT in a mouse model of MS and identify a myeloid transcriptional signature associated with neuroprotection.
引用
收藏
页码:901 / 912
页数:12
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