PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas

Navarro, Judith; Gozalbo-López, Beatriz; Méndez, Andrea C.; Dantzer, Françoise; Schreiber, Valérie; Martínez, Carlos; Arana, David M.; Farrés, Jordi; Revilla-Nuin, Beatriz; Bueno, María F.; Ampurdanés, Coral; Galindo-Campos, Miguel A.; Knobel, Philip A.; Segura-Bayona, Sandra; Martín Caballero, Juan; Stracker, Travis; Aparicio, Pedro; Del Val, Margarita; Yélamos López, José

PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas

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dc.contributor.author Navarro, Judithca
dc.contributor.author Gozalbo-López, Beatrizca
dc.contributor.author Méndez, Andrea C.ca
dc.contributor.author Dantzer, Françoiseca
dc.contributor.author Schreiber, Valérieca
dc.contributor.author Martínez, Carlosca
dc.contributor.author Arana, David M.ca
dc.contributor.author Farrés, Jordica
dc.contributor.author Revilla-Nuin, Beatrizca
dc.contributor.author Bueno, María F.ca
dc.contributor.author Ampurdanés, Coralca
dc.contributor.author Galindo-Campos, Miguel A.ca
dc.contributor.author Knobel, Philip A.ca
dc.contributor.author Segura-Bayona, Sandraca
dc.contributor.author Martín Caballero, Juanca
dc.contributor.author Stracker, Travisca
dc.contributor.author Aparicio, Pedroca
dc.contributor.author Del Val, Margaritaca
dc.contributor.author Yélamos López, Joséca
dc.date.accessioned 2018-03-06T08:11:11Z
dc.date.available 2018-03-06T08:11:11Z
dc.date.issued 2017
dc.description.abstract The maintenance of T-cell homeostasis must be tightly regulated. Here, we have identified a coordinated role of Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in maintaining T-lymphocyte number and function. Mice bearing a T-cell specific deficiency of PARP-2 in a PARP-1-deficient background showed defective thymocyte maturation and diminished numbers of peripheral CD4+ and CD8+ T-cells. Meanwhile, peripheral T-cell number was not affected in single PARP-1 or PARP-2-deficient mice. T-cell lymphopenia was associated with dampened in vivo immune responses to synthetic T-dependent antigens and virus, increased DNA damage and T-cell death. Moreover, double-deficiency in PARP-1/PARP-2 in T-cells led to highly aggressive T-cell lymphomas with long latency. Our findings establish a coordinated role of PARP-1 and PARP-2 in T-cell homeostasis that might impact on the development of PARP-centred therapies.
dc.description.sponsorship The JY, MDV and THS laboratories are supported by grants from Spanish Ministerio de Economía y Competitividad (MINECO) (SAF2014-53467-R to JY; SAF2010-18917 and SAF2013-48754-C2-1-R to MDV; and BFU2015-68354 to THS), cofinanced by the European Regional Development Fund, Fundació La Marató de TV3 (20134130), and CIBERehd. ACM is supported by a Formación de Doctores predoctoral contract from MINECO, THS by Ayudas para incentivar la incorporación estable de doctores 2015 (MINECO), PAK by an Advanced Postdoc Mobility fellowship from the Swiss National Science Foundation and SSB by a predoctoral fellowship from Fundació La Caixa
dc.format.mimetype application/pdf
dc.identifier.citation Navarro J, Gozalbo-López B, Méndez AC, Dantzer F, Schreiber V, Martínez C. et al. PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas. Sci Rep. 2017 Feb 9;7:41962. DOI: 10.1038/srep41962
dc.identifier.doi http://dx.doi.org/10.1038/srep41962
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10230/34049
dc.language.iso eng
dc.publisher Nature Publishing Groupca
dc.relation.ispartof Scientific Reports. 2017 Feb 9;7:41962
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-53467-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-18917
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-48754-C2-1-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68354
dc.rights Copyright © 2017, The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Limfomes -- Tractament
dc.title PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomasca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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