Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis

Marius Marc-Daniel Mader; Alan Napole; Danwei Wu; Micaiah Atkins; Alexa Scavetti; Yohei Shibuya; Aulden Foltz; Oliver Hahn; Yongjin Yoo; Ron Danziger; Christina Tan; Tony Wyss-Coray; Lawrence Steinman; Marius Wernig

doi:10.1038/s41593-024-01609-3

Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis

Nat Neurosci. 2024 Mar 21. doi: 10.1038/s41593-024-01609-3. Online ahead of print.

Authors

Marius Marc-Daniel Mader^{1 2}, Alan Napole^#^{1 2}, Danwei Wu^#^{1 2 3}, Micaiah Atkins⁴, Alexa Scavetti^{1 2}, Yohei Shibuya^{1 2}, Aulden Foltz⁴, Oliver Hahn⁴, Yongjin Yoo^{1 2}, Ron Danziger^{1 2}, Christina Tan^{1 2}, Tony Wyss-Coray⁴, Lawrence Steinman³, Marius Wernig^{5 6}

Affiliations

¹ Institute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
³ Department of Neurology and Neurosciences, Division of Neuroimmunology and Multiple Sclerosis Center, Stanford University of Medicine, Stanford, CA, USA.
⁴ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Institute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. wernig@stanford.edu.
⁶ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. wernig@stanford.edu.

^# Contributed equally.

PMID: 38514857
DOI: 10.1038/s41593-024-01609-3

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.

Abstract

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