Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.

<h4>Background</h4>Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS) in health and disease. Here, we hypothesized that neurodegenerative diseases might be ass...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ilan Vaknin, Gilad Kunis, Omer Miller, Oleg Butovsky, Shay Bukshpan, David R Beers, Jenny S Henkel, Eti Yoles, Stanley H Appel, Michal Schwartz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/229b39d1adf24f5281f19de1c1c36e4f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:229b39d1adf24f5281f19de1c1c36e4f
record_format	dspace
spelling	oai:doaj.org-article:229b39d1adf24f5281f19de1c1c36e4f2021-11-18T07:35:03ZExcess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.1932-620310.1371/journal.pone.0026921https://doaj.org/article/229b39d1adf24f5281f19de1c1c36e4f2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22073221/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS) in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs), representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease.<h4>Methods and findings</h4>We tested this working hypothesis in amyotrophic lateral sclerosis (ALS) and its mouse model, which are characterized by a rapid progression once clinical symptoms are evident. Adaptive transfer of alternatively activated myeloid (M2) cells, which homed to the spleen and exhibited immune suppressive activity in G93A mutant superoxide dismutase-1 (mSOD1) mice at a stage before emergence of disease symptoms, resulted in earlier appearance of disease symptoms and shorter life expectancy. The same protocol mitigated the inflammation-induced disease model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), which requires circulating T cells for disease induction. Analysis of whole peripheral blood samples obtained from 28 patients suffering from sporadic ALS (sALS), revealed a two-fold increase in the percentage of circulating MDSCs (LIN(-/Low)HLA-DR(-)CD33(+)) compared to controls.<h4>Conclusions</h4>Taken together, these results emphasize the distinct requirements for fighting the inflammatory neurodegenerative disease, multiple sclerosis, and the neurodegenerative disease, ALS, though both share a local inflammatory component. Moreover, the increased levels of circulating MDSCs in ALS patients indicates the operation of systemic mechanisms that might lead to an impairment of T cell reactivity needed to overcome the disease conditions within the CNS. This high level of suppressive immune cells might represent a risk factor and a novel target for therapeutic intervention in ALS at least at the early stage.Ilan VakninGilad KunisOmer MillerOleg ButovskyShay BukshpanDavid R BeersJenny S HenkelEti YolesStanley H AppelMichal SchwartzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e26921 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ilan Vaknin Gilad Kunis Omer Miller Oleg Butovsky Shay Bukshpan David R Beers Jenny S Henkel Eti Yoles Stanley H Appel Michal Schwartz Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.
description	<h4>Background</h4>Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS) in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs), representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease.<h4>Methods and findings</h4>We tested this working hypothesis in amyotrophic lateral sclerosis (ALS) and its mouse model, which are characterized by a rapid progression once clinical symptoms are evident. Adaptive transfer of alternatively activated myeloid (M2) cells, which homed to the spleen and exhibited immune suppressive activity in G93A mutant superoxide dismutase-1 (mSOD1) mice at a stage before emergence of disease symptoms, resulted in earlier appearance of disease symptoms and shorter life expectancy. The same protocol mitigated the inflammation-induced disease model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), which requires circulating T cells for disease induction. Analysis of whole peripheral blood samples obtained from 28 patients suffering from sporadic ALS (sALS), revealed a two-fold increase in the percentage of circulating MDSCs (LIN(-/Low)HLA-DR(-)CD33(+)) compared to controls.<h4>Conclusions</h4>Taken together, these results emphasize the distinct requirements for fighting the inflammatory neurodegenerative disease, multiple sclerosis, and the neurodegenerative disease, ALS, though both share a local inflammatory component. Moreover, the increased levels of circulating MDSCs in ALS patients indicates the operation of systemic mechanisms that might lead to an impairment of T cell reactivity needed to overcome the disease conditions within the CNS. This high level of suppressive immune cells might represent a risk factor and a novel target for therapeutic intervention in ALS at least at the early stage.
format	article
author	Ilan Vaknin Gilad Kunis Omer Miller Oleg Butovsky Shay Bukshpan David R Beers Jenny S Henkel Eti Yoles Stanley H Appel Michal Schwartz
author_facet	Ilan Vaknin Gilad Kunis Omer Miller Oleg Butovsky Shay Bukshpan David R Beers Jenny S Henkel Eti Yoles Stanley H Appel Michal Schwartz
author_sort	Ilan Vaknin
title	Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.
title_short	Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.
title_full	Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.
title_fullStr	Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.
title_full_unstemmed	Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.
title_sort	excess circulating alternatively activated myeloid (m2) cells accelerate als progression while inhibiting experimental autoimmune encephalomyelitis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/229b39d1adf24f5281f19de1c1c36e4f
work_keys_str_mv	AT ilanvaknin excesscirculatingalternativelyactivatedmyeloidm2cellsacceleratealsprogressionwhileinhibitingexperimentalautoimmuneencephalomyelitis AT giladkunis excesscirculatingalternativelyactivatedmyeloidm2cellsacceleratealsprogressionwhileinhibitingexperimentalautoimmuneencephalomyelitis AT omermiller excesscirculatingalternativelyactivatedmyeloidm2cellsacceleratealsprogressionwhileinhibitingexperimentalautoimmuneencephalomyelitis AT olegbutovsky excesscirculatingalternativelyactivatedmyeloidm2cellsacceleratealsprogressionwhileinhibitingexperimentalautoimmuneencephalomyelitis AT shaybukshpan excesscirculatingalternativelyactivatedmyeloidm2cellsacceleratealsprogressionwhileinhibitingexperimentalautoimmuneencephalomyelitis AT davidrbeers excesscirculatingalternativelyactivatedmyeloidm2cellsacceleratealsprogressionwhileinhibitingexperimentalautoimmuneencephalomyelitis AT jennyshenkel excesscirculatingalternativelyactivatedmyeloidm2cellsacceleratealsprogressionwhileinhibitingexperimentalautoimmuneencephalomyelitis AT etiyoles excesscirculatingalternativelyactivatedmyeloidm2cellsacceleratealsprogressionwhileinhibitingexperimentalautoimmuneencephalomyelitis AT stanleyhappel excesscirculatingalternativelyactivatedmyeloidm2cellsacceleratealsprogressionwhileinhibitingexperimentalautoimmuneencephalomyelitis AT michalschwartz excesscirculatingalternativelyactivatedmyeloidm2cellsacceleratealsprogressionwhileinhibitingexperimentalautoimmuneencephalomyelitis
_version_	1718423209300197376

Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.

Ejemplares similares