E2f2 Attenuates Apoptosis of Activated T Lymphocytes and Protects from Immune-Mediated Injury through Repression of Fas and FasL
dc.contributor.author | Mustafa, Noor | |
dc.contributor.author | Michelena Sánchez, Jone | |
dc.contributor.author | Infante, Arantza | |
dc.contributor.author | Zenarruzabeitia, Olatz | |
dc.contributor.author | Eriz Micieces, Ainhoa | |
dc.contributor.author | Iglesias Ara, Ainhoa | |
dc.contributor.author | Zubiaga Elordieta, Ana María | |
dc.date.accessioned | 2022-01-13T12:33:15Z | |
dc.date.available | 2022-01-13T12:33:15Z | |
dc.date.issued | 2021-12-28 | |
dc.identifier.citation | International Journal of Molecular Sciences 23(1) : (2022) // Article ID 311 | es_ES |
dc.identifier.issn | 1422-0067 | |
dc.identifier.uri | http://hdl.handle.net/10810/54945 | |
dc.description.abstract | Targeted disruption of E2f2 in mice causes T-cell hyperactivation and a disproportionate cell cycle entry upon stimulation. However, E2f2−/− mice do not develop a lymphoproliferative condition. We report that E2f2 plays a Fas-dependent anti-apoptotic function in vitro and in vivo. TCR-stimulated murine E2f2−/− T cells overexpress the proapoptotic genes Fas and FasL and exhibit enhanced apoptosis, which is prevented by treatment with neutralizing anti-FasL antibodies. p53 pathway is activated in TCR-stimulated E2f2−/− lymphocytes, but targeted disruption of p53 in E2f2−/− mice does not abrogate Fas/FasL expression or apoptosis, implying a p53-independent apoptotic mechanism. We show that E2f2 is recruited to Fas and FasL gene promoters to repress their expression. in vivo, E2f2−/− mice are prone to develop immune-mediated liver injury owing to an aberrant lymphoid Fas/FasL activation. Taken together, our results suggest that E2f2-dependent inhibition of Fas/FasL pathway may play a direct role in limiting the development of immune-mediated pathologies | es_ES |
dc.description.sponsorship | This work was supported by grants from the MCIU/AEI/FEDER, UE (RTI2018-097497-B-100 and RED2018-102723-T) and Basque Government, Department of Education (IT1257-19) to A.M.Z. N.M. is recipient of a University of the Basque Country (UPV/EHU) Postdoctoral Fellowship. J.M. is recipient of an Ikerbasque Research Foundation Fellowship. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/RTI2018-097497-B-100 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/RED2018-102723-T | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | E2f | es_ES |
dc.subject | apoptosis | es_ES |
dc.subject | Fas | es_ES |
dc.subject | FasL | es_ES |
dc.subject | T lymphocytes | es_ES |
dc.subject | immune disorder | es_ES |
dc.title | E2f2 Attenuates Apoptosis of Activated T Lymphocytes and Protects from Immune-Mediated Injury through Repression of Fas and FasL | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2022-01-10T14:38:04Z | |
dc.rights.holder | 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1422-0067/23/1/311/htm | es_ES |
dc.identifier.doi | 10.3390/ijms23010311 | |
dc.departamentoes | Genética, antropología física y fisiología animal | |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia |
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Except where otherwise noted, this item's license is described as 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).