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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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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. |
format | Online Article Text |
id | pubmed-10028976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
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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