Artículo
Chaperoned amyloid proteins for immune manipulation: a-Synuclein/Hsp70 shifts immunity toward a modulatory phenotype
Autor/es | Labrador Garrido, Adahir
Cejudo Guillén, Marta Klippstein Martin, Rebecca Genst, Erwin J. de Tomas Gallardo, Laura Leal, María M. Pozo Pérez, David |
Departamento | Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología |
Fecha de publicación | 2014 |
Fecha de depósito | 2017-09-08 |
Publicado en |
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Resumen | 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, ... 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. |
Identificador del proyecto | info:eu-repo/grantAgreement/MINECO/SAF-2012/39720
P10-CTS-6928 P11-CTS-8161 |
Cita | 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. |
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