Hsp70 regulates immune response in experimental autoimmune encephalomyelitis.

Heat shock protein (Hsp)70 is one of the most important stress-inducible proteins. Intracellular Hsp70 not only mediates chaperone-cytoprotective functions but can also block multiple steps in the apoptosis pathway. In addition, Hsp70 is actively released into the extracellular milieu, thereby promo...

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Autores principales:	M José Mansilla, Carme Costa, Herena Eixarch, Vanja Tepavcevic, Mireia Castillo, Roland Martin, Catherine Lubetzki, Marie-Stéphane Aigrot, Xavier Montalban, Carmen Espejo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/66262104b8724bafb11283defd092b40
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spelling	oai:doaj.org-article:66262104b8724bafb11283defd092b402021-11-25T06:03:17ZHsp70 regulates immune response in experimental autoimmune encephalomyelitis.1932-620310.1371/journal.pone.0105737https://doaj.org/article/66262104b8724bafb11283defd092b402014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25153885/?tool=EBIhttps://doaj.org/toc/1932-6203Heat shock protein (Hsp)70 is one of the most important stress-inducible proteins. Intracellular Hsp70 not only mediates chaperone-cytoprotective functions but can also block multiple steps in the apoptosis pathway. In addition, Hsp70 is actively released into the extracellular milieu, thereby promoting innate and adaptive immune responses. Thus, Hsp70 may be a critical molecule in multiple sclerosis (MS) pathogenesis and a potential target in this disease due to its immunological and cytoprotective functions. To investigate the role of Hsp70 in MS pathogenesis, we examined its immune and cytoprotective roles using both in vitro and in vivo experimental procedures. We found that Hsp70.1-deficient mice were more resistant to developing experimental autoimmune encephalomyelitis (EAE) compared with their wild-type (WT) littermates, suggesting that Hsp70.1 plays a critical role in promoting an effective myelin oligodendrocyte glycoprotein (MOG)-specific T cell response. Conversely, Hsp70.1-deficient mice that developed EAE showed an increased level of autoreactive T cells to achieve the same production of cytokines compared with the WT mice. Although a neuroprotective role of HSP70 has been suggested, Hsp70.1-deficient mice that developed EAE did not exhibit increased demyelination compared with the control mice. Accordingly, Hsp70 deficiency did not influence the vulnerability to apoptosis of oligodendrocyte precursor cells (OPCs) in culture. Thus, the immunological role of Hsp70 may be relevant in EAE, and specific therapies down-regulating Hsp70 expression may be a promising approach to reduce the early autoimmune response in MS patients.M José MansillaCarme CostaHerena EixarchVanja TepavcevicMireia CastilloRoland MartinCatherine LubetzkiMarie-Stéphane AigrotXavier MontalbanCarmen EspejoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e105737 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M José Mansilla Carme Costa Herena Eixarch Vanja Tepavcevic Mireia Castillo Roland Martin Catherine Lubetzki Marie-Stéphane Aigrot Xavier Montalban Carmen Espejo Hsp70 regulates immune response in experimental autoimmune encephalomyelitis.
description	Heat shock protein (Hsp)70 is one of the most important stress-inducible proteins. Intracellular Hsp70 not only mediates chaperone-cytoprotective functions but can also block multiple steps in the apoptosis pathway. In addition, Hsp70 is actively released into the extracellular milieu, thereby promoting innate and adaptive immune responses. Thus, Hsp70 may be a critical molecule in multiple sclerosis (MS) pathogenesis and a potential target in this disease due to its immunological and cytoprotective functions. To investigate the role of Hsp70 in MS pathogenesis, we examined its immune and cytoprotective roles using both in vitro and in vivo experimental procedures. We found that Hsp70.1-deficient mice were more resistant to developing experimental autoimmune encephalomyelitis (EAE) compared with their wild-type (WT) littermates, suggesting that Hsp70.1 plays a critical role in promoting an effective myelin oligodendrocyte glycoprotein (MOG)-specific T cell response. Conversely, Hsp70.1-deficient mice that developed EAE showed an increased level of autoreactive T cells to achieve the same production of cytokines compared with the WT mice. Although a neuroprotective role of HSP70 has been suggested, Hsp70.1-deficient mice that developed EAE did not exhibit increased demyelination compared with the control mice. Accordingly, Hsp70 deficiency did not influence the vulnerability to apoptosis of oligodendrocyte precursor cells (OPCs) in culture. Thus, the immunological role of Hsp70 may be relevant in EAE, and specific therapies down-regulating Hsp70 expression may be a promising approach to reduce the early autoimmune response in MS patients.
format	article
author	M José Mansilla Carme Costa Herena Eixarch Vanja Tepavcevic Mireia Castillo Roland Martin Catherine Lubetzki Marie-Stéphane Aigrot Xavier Montalban Carmen Espejo
author_facet	M José Mansilla Carme Costa Herena Eixarch Vanja Tepavcevic Mireia Castillo Roland Martin Catherine Lubetzki Marie-Stéphane Aigrot Xavier Montalban Carmen Espejo
author_sort	M José Mansilla
title	Hsp70 regulates immune response in experimental autoimmune encephalomyelitis.
title_short	Hsp70 regulates immune response in experimental autoimmune encephalomyelitis.
title_full	Hsp70 regulates immune response in experimental autoimmune encephalomyelitis.
title_fullStr	Hsp70 regulates immune response in experimental autoimmune encephalomyelitis.
title_full_unstemmed	Hsp70 regulates immune response in experimental autoimmune encephalomyelitis.
title_sort	hsp70 regulates immune response in experimental autoimmune encephalomyelitis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/66262104b8724bafb11283defd092b40
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Hsp70 regulates immune response in experimental autoimmune encephalomyelitis.

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