dc.creator | Labrador Garrido, Adahir | es |
dc.creator | Cejudo Guillén, Marta | es |
dc.creator | Klippstein Martin, Rebecca | es |
dc.creator | Genst, Erwin J. de | es |
dc.creator | Tomas Gallardo, Laura | es |
dc.creator | Leal, María M. | es |
dc.creator | Pozo Pérez, David | es |
dc.date.accessioned | 2017-09-08T11:37:45Z | |
dc.date.available | 2017-09-08T11:37:45Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Labrador Garrido, A., Cejudo Guillén, M., Klippstein Martin, R., Genst, E.J.D., Tomas Gallardo, L., Leal, M.M. y Pozo Pérez, D. (2014). Chaperoned amyloid proteins for immune manipulation: a-Synuclein/Hsp70 shifts immunity toward a modulatory phenotype. Immunity, Inflammation and Disease, 2 (4), 226-238. | |
dc.identifier.issn | 2050-4527 | es |
dc.identifier.uri | http://hdl.handle.net/11441/64290 | |
dc.description.abstract | α-Synuclein (αSyn) is a 140-residue amyloid-forming protein whose aggregation is linked to Parkinson's disease (PD). It has also been found to play a critical role in the immune imbalance that accompanies disease progression, a characteristic that has prompted the search for an effective αSyn-based immunotherapy. In this study, we have simultaneously exploited two important features of certain heat-shock proteins (HSPs): their classical “chaperone” activities and their recently discovered and diverse “immunoactive” properties. In particular, we have explored the immune response elicited by immunization of C57BL/6 mice with an αSyn/Hsp70 protein combination in the absence of added adjuvant. Our results show differential effects for mice immunized with the αSyn/Hsp70 complex, including a restrained αSyn-specific (IgM and IgG) humoral response as well as minimized alterations in the Treg (CD4+CD25+Foxp3+) and Teff (CD4+Foxp3−) cell populations, as opposed to significant changes in mice immunized with αSyn and Hsp70 alone. Furthermore, in vitro-stimulated splenocytes from immunized mice showed the lowest relative response against αSyn challenge for the “αSyn/Hsp70” experimental group as measured by IFN-γ and IL-17 secretion, and higher IL-10 levels when stimulated with LPS. Finally, serum levels of Th1-cytokine IFN-γ and immunomodulatory IL-10 indicated a unique shift toward an immunomodulatory/immunoprotective phenotype in mice immunized with the αSyn/Hsp70 complex. Overall, we propose the use of functional “HSP-chaperoned amyloid/aggregating proteins” generated with appropriate HSP-substrate protein combinations, such as the αSyn/Hsp70 complex, as a novel strategy for immune-based intervention against synucleinopathies and other amyloid or “misfolding” neurodegenerative disorders. | es |
dc.description.sponsorship | España, Ministerio de Economía y Competitividad SAF-2012/39720 | es |
dc.description.sponsorship | Junta de Andalucía P10-CTS-6928 | es |
dc.description.sponsorship | Junta de Andalucía P11-CTS-8161 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Wiley Open Access | es |
dc.relation.ispartof | Immunity, Inflammation and Disease, 2 (4), 226-238. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | heat-shock proteins (HSPs) | es |
dc.subject | amyloid disease | es |
dc.subject | immunization | es |
dc.subject | immunomodulation | es |
dc.subject | α-synuclein | es |
dc.title | Chaperoned amyloid proteins for immune manipulation: a-Synuclein/Hsp70 shifts immunity toward a modulatory phenotype | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología | es |
dc.relation.projectID | info:eu-repo/grantAgreement/MINECO/SAF-2012/39720 | es |
dc.relation.projectID | P10-CTS-6928 | es |
dc.relation.projectID | P11-CTS-8161 | es |
dc.relation.publisherversion | http://dx.doi.org/ 10.1002/iid3.39 | es |
dc.identifier.doi | 10.1002/iid3.39 | es |
idus.format.extent | 8 p. | es |
dc.journaltitle | Immunity, Inflammation and Disease | es |
dc.publication.volumen | 2 | es |
dc.publication.issue | 4 | es |
dc.publication.initialPage | 226 | es |
dc.publication.endPage | 238 | es |