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Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation

Multiple sclerosis (MS) is an autoimmune disease associated with inflammatory demyelination in the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) is under investigation as a promising therapy for treatment-refractory MS. Here we identify a reactive myeloid state in...

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Autores principales: Mader, Marius Marc-Daniel, Napole, Alan, Wu, Danwei, Shibuya, Yohei, Scavetti, Alexa, Foltz, Aulden, Atkins, Micaiah, Hahn, Oliver, Yoo, Yongjin, Danziger, Ron, Tan, Christina, Wyss-Coray, Tony, Steinman, Lawrence, Wernig, Marius
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10028976/
https://www.ncbi.nlm.nih.gov/pubmed/36945385
http://dx.doi.org/10.1101/2023.03.10.532123
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author Mader, Marius Marc-Daniel
Napole, Alan
Wu, Danwei
Shibuya, Yohei
Scavetti, Alexa
Foltz, Aulden
Atkins, Micaiah
Hahn, Oliver
Yoo, Yongjin
Danziger, Ron
Tan, Christina
Wyss-Coray, Tony
Steinman, Lawrence
Wernig, Marius
author_facet Mader, Marius Marc-Daniel
Napole, Alan
Wu, Danwei
Shibuya, Yohei
Scavetti, Alexa
Foltz, Aulden
Atkins, Micaiah
Hahn, Oliver
Yoo, Yongjin
Danziger, Ron
Tan, Christina
Wyss-Coray, Tony
Steinman, Lawrence
Wernig, Marius
author_sort Mader, Marius Marc-Daniel
collection PubMed
description Multiple sclerosis (MS) is an autoimmune disease associated with inflammatory demyelination in the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) is under investigation as a promising therapy for treatment-refractory MS. Here we identify a reactive myeloid state in chronic experimental autoimmune encephalitis (EAE) mice and MS patients that is surprisingly associated with neuroprotection and immune suppression. HCT in EAE mice leads to an enhancement of this myeloid state, as well as clinical improvement, reduction of demyelinated lesions, suppression of cytotoxic T cells, and amelioration of reactive astrogliosis reflected in reduced expression of EAE-associated gene signatures in oligodendrocytes and astrocytes. Further enhancement of myeloid cell incorporation into the CNS following a modified HCT protocol results in an even more consistent therapeutic effect corroborated by additional amplification of HCT-induced transcriptional changes, underlining myeloid-derived beneficial effects in the chronic phase of EAE. Replacement or manipulation of CNS myeloid cells thus represents an intriguing therapeutic direction for inflammatory demyelinating disease.
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spelling pubmed-100289762023-03-22 Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation Mader, Marius Marc-Daniel Napole, Alan Wu, Danwei Shibuya, Yohei Scavetti, Alexa Foltz, Aulden Atkins, Micaiah Hahn, Oliver Yoo, Yongjin Danziger, Ron Tan, Christina Wyss-Coray, Tony Steinman, Lawrence Wernig, Marius bioRxiv Article Multiple sclerosis (MS) is an autoimmune disease associated with inflammatory demyelination in the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) is under investigation as a promising therapy for treatment-refractory MS. Here we identify a reactive myeloid state in chronic experimental autoimmune encephalitis (EAE) mice and MS patients that is surprisingly associated with neuroprotection and immune suppression. HCT in EAE mice leads to an enhancement of this myeloid state, as well as clinical improvement, reduction of demyelinated lesions, suppression of cytotoxic T cells, and amelioration of reactive astrogliosis reflected in reduced expression of EAE-associated gene signatures in oligodendrocytes and astrocytes. Further enhancement of myeloid cell incorporation into the CNS following a modified HCT protocol results in an even more consistent therapeutic effect corroborated by additional amplification of HCT-induced transcriptional changes, underlining myeloid-derived beneficial effects in the chronic phase of EAE. Replacement or manipulation of CNS myeloid cells thus represents an intriguing therapeutic direction for inflammatory demyelinating disease. Cold Spring Harbor Laboratory 2023-03-12 /pmc/articles/PMC10028976/ /pubmed/36945385 http://dx.doi.org/10.1101/2023.03.10.532123 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Mader, Marius Marc-Daniel
Napole, Alan
Wu, Danwei
Shibuya, Yohei
Scavetti, Alexa
Foltz, Aulden
Atkins, Micaiah
Hahn, Oliver
Yoo, Yongjin
Danziger, Ron
Tan, Christina
Wyss-Coray, Tony
Steinman, Lawrence
Wernig, Marius
Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation
title Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation
title_full Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation
title_fullStr Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation
title_full_unstemmed Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation
title_short Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation
title_sort augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10028976/
https://www.ncbi.nlm.nih.gov/pubmed/36945385
http://dx.doi.org/10.1101/2023.03.10.532123
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