Erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE.

<h4>Background</h4>Beneficial effects of short-term erythropoietin (EPO) therapy have been demonstrated in several animal models of acute neurologic injury, including experimental autoimmune encephalomyelitis (EAE)--the animal model of multiple sclerosis. We have found that EPO treatment...

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Autores principales:	RuiRong Yuan, Yasuhiro Maeda, Weiping Li, Wei Lu, Stuart Cook, Peter Dowling
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e05c479295244a3a92913d5c11b788fd
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spelling	oai:doaj.org-article:e05c479295244a3a92913d5c11b788fd2021-11-25T06:12:53ZErythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE.1932-620310.1371/journal.pone.0001924https://doaj.org/article/e05c479295244a3a92913d5c11b788fd2008-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18382691/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Beneficial effects of short-term erythropoietin (EPO) therapy have been demonstrated in several animal models of acute neurologic injury, including experimental autoimmune encephalomyelitis (EAE)--the animal model of multiple sclerosis. We have found that EPO treatment substantially reduces the acute clinical paralysis seen in EAE mice and this improvement is accompanied by a large reduction in the mononuclear cell infiltration and downregulation of glial MHC class II expression within the inflamed CNS. Other reports have recently indicated that peripherally generated anti-inflammatory CD4(+)Foxp3(+) regulatory T cells (Tregs) and the IL17-producing CD4+ T helper cell (Th17) subpopulations play key antagonistic roles in EAE pathogenesis. However, no information regarding the effects of EPO therapy on the behavior of the general mononuclear-lymphocyte population, Tregs or Th17 cells in EAE has emerged.<h4>Methods and findings</h4>We first determined in vivo that EPO therapy markedly suppressed MOG specific T cell proliferation and sharply reduced the number of reactive dendritic cells (CD11c positive) in EAE lymph nodes during both inductive and later symptomatic phases of MOG(35-55) induced EAE. We then determined the effect in vivo of EPO on numbers of peripheral Treg cells and Th17 cells. We found that EPO treatment modulated immune balance in both the periphery and the inflamed spinal cord by promoting a large expansion in Treg cells, inhibiting Th17 polarization and abrogating proliferation of the antigen presenting dendritic cell population. Finally we utilized tissue culture assays to show that exposure to EPO in vitro similarly downregulated MOG-specific T cell proliferation and also greatly suppressed T cell production of pro-inflammatory cytokines.<h4>Conclusions</h4>Taken together, our findings reveal an important new locus whereby EPO induces substantial long-term tissue protection in the host through signaling to several critical subsets of immune cells that reside in the peripheral lymphatic system.RuiRong YuanYasuhiro MaedaWeiping LiWei LuStuart CookPeter DowlingPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 4, p e1924 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q RuiRong Yuan Yasuhiro Maeda Weiping Li Wei Lu Stuart Cook Peter Dowling Erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE.
description	<h4>Background</h4>Beneficial effects of short-term erythropoietin (EPO) therapy have been demonstrated in several animal models of acute neurologic injury, including experimental autoimmune encephalomyelitis (EAE)--the animal model of multiple sclerosis. We have found that EPO treatment substantially reduces the acute clinical paralysis seen in EAE mice and this improvement is accompanied by a large reduction in the mononuclear cell infiltration and downregulation of glial MHC class II expression within the inflamed CNS. Other reports have recently indicated that peripherally generated anti-inflammatory CD4(+)Foxp3(+) regulatory T cells (Tregs) and the IL17-producing CD4+ T helper cell (Th17) subpopulations play key antagonistic roles in EAE pathogenesis. However, no information regarding the effects of EPO therapy on the behavior of the general mononuclear-lymphocyte population, Tregs or Th17 cells in EAE has emerged.<h4>Methods and findings</h4>We first determined in vivo that EPO therapy markedly suppressed MOG specific T cell proliferation and sharply reduced the number of reactive dendritic cells (CD11c positive) in EAE lymph nodes during both inductive and later symptomatic phases of MOG(35-55) induced EAE. We then determined the effect in vivo of EPO on numbers of peripheral Treg cells and Th17 cells. We found that EPO treatment modulated immune balance in both the periphery and the inflamed spinal cord by promoting a large expansion in Treg cells, inhibiting Th17 polarization and abrogating proliferation of the antigen presenting dendritic cell population. Finally we utilized tissue culture assays to show that exposure to EPO in vitro similarly downregulated MOG-specific T cell proliferation and also greatly suppressed T cell production of pro-inflammatory cytokines.<h4>Conclusions</h4>Taken together, our findings reveal an important new locus whereby EPO induces substantial long-term tissue protection in the host through signaling to several critical subsets of immune cells that reside in the peripheral lymphatic system.
format	article
author	RuiRong Yuan Yasuhiro Maeda Weiping Li Wei Lu Stuart Cook Peter Dowling
author_facet	RuiRong Yuan Yasuhiro Maeda Weiping Li Wei Lu Stuart Cook Peter Dowling
author_sort	RuiRong Yuan
title	Erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE.
title_short	Erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE.
title_full	Erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE.
title_fullStr	Erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE.
title_full_unstemmed	Erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE.
title_sort	erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune eae.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/e05c479295244a3a92913d5c11b788fd
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Erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE.

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