title: Hsp70 regulates immune response in experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra, Cerdanyola del Vallès, Barcelona, Spain.
authors.forename: M José
authors.initials: MJ
authors.lastname: Mansilla
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra, Cerdanyola del Vallès, Barcelona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Costa
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra, Cerdanyola del Vallès, Barcelona, Spain.
authors.forename: Herena
authors.initials: H
authors.lastname: Eixarch
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, UM-75, ICM-GH Pitié-Salpêtrière, Paris, France, Inserm, U1127, Paris, France, CNRS, UMR 7225, Paris, France.
authors.forename: Vanja
authors.initials: V
authors.lastname: Tepavcevic
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra, Cerdanyola del Vallès, Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Castillo
authors.affiliation: Department of Neuroimmunology and Multiple Sclerosis Research, Neurology Clinic, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, UM-75, ICM-GH Pitié-Salpêtrière, Paris, France, Inserm, U1127, Paris, France, CNRS, UMR 7225, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, UM-75, ICM-GH Pitié-Salpêtrière, Paris, France, Inserm, U1127, Paris, France, CNRS, UMR 7225, Paris, France.
authors.forename: Marie-Stéphane
authors.initials: MS
authors.lastname: Aigrot
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra, Cerdanyola del Vallès, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra, Cerdanyola del Vallès, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Espejo
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D049109:Cell Proliferation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein