Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis.
Nat Neurosci
; 27(5): 901-912, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38514857
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myeloid Cells
/
Encephalomyelitis, Autoimmune, Experimental
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Mice, Inbred C57BL
Limits:
Animals
Language:
En
Journal:
Nat Neurosci
Journal subject:
NEUROLOGIA
Year:
2024
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA