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dc.contributor.authorJiménez-Fernández, María
dc.contributor.authorRodríguez-Sinovas, Cristina
dc.contributor.authorCañes, Laia
dc.contributor.authorBallester-Servera, Carme
dc.contributor.authorVara, Alicia
dc.contributor.authorRequena, Silvia
dc.contributor.authorde la Fuente, Hortensia 
dc.contributor.authorMartínez-González, José
dc.contributor.authorSánchez-Madrid, Francisco
dc.identifier.citationCell Mol Life Sci. 2022 Aug 5;79(8):468es_ES
dc.description.abstractThe mechanisms that control the inflammatory-immune response play a key role in tissue remodelling in cardiovascular diseases. T cell activation receptor CD69 binds to oxidized low-density lipoprotein (oxLDL), inducing the expression of anti-inflammatory NR4A nuclear receptors and modulating inflammation in atherosclerosis. To understand the downstream T cell responses triggered by the CD69-oxLDL binding, we incubated CD69-expressing Jurkat T cells with oxLDL. RNA sequencing revealed a differential gene expression profile dependent on the presence of CD69 and the degree of LDL oxidation. CD69-oxLDL binding induced the expression of NR4A receptors (NR4A1 and NR4A3), but also of PD-1. These results were confirmed using oxLDL and a monoclonal antibody against CD69 in CD69-expressing Jurkat and primary CD4 + lymphocytes. CD69-mediated induction of PD-1 and NR4A3 was dependent on NFAT activation. Silencing NR4A3 slightly increased PD-1 levels, suggesting a potential regulation of PD-1 by this receptor. Moreover, expression of PD-1, CD69 and NR4A3 was increased in human arteries with chronic inflammation compared to healthy controls, with a strong correlation between PD-1 and CD69 mRNA expression (r = 0.655 P < 0.0001). Moreover, PD-1 was expressed in areas enriched in CD3 infiltrating T cells. Our results underscore a novel mechanism of PD-1 induction independent of TCR signalling that might contribute to the role of CD69 in the modulation of inflammation and vascular remodelling in cardiovascular diseases.es_ES
dc.description.sponsorshipOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grant S2017/BMD-3671-INFLAMUNE-CM from the Comunidad de Madrid, a grant from the Ramón Areces Foundation “Ciencias de la Vida y la Salud”, “La Caixa” Banking Foundation (HR17-00016) to FSM; grants PDC2021-121719-I00 and PDI-2020-120412RBI00 to FSM, and RTI2018-094727-B-100 to JMG funded by MCIN/ AEI/10.13039/501100011033 and by “ERDF A way of making Europe”; the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR-00333) to JMG; and a grant from the Instituto de Salud Carlos III (PI18/0919) to CR. M. Jiménez-Fernández is supported by a FPI-Severo Ochoa-CNIC (PRE2019-087941); C. Ballester-Servera is supported by a FPU fellowship (Ministerio de Universidades).es_ES
dc.publisherSpringer es_ES
dc.subject.meshCardiovascular Diseases es_ES
dc.subject.meshProgrammed Cell Death 1 Receptor es_ES
dc.subject.meshAntigens, CD es_ES
dc.subject.meshAntigens, Differentiation, T-Lymphocyte es_ES
dc.subject.meshApoptosis es_ES
dc.subject.meshCD4-Positive T-Lymphocytes es_ES
dc.subject.meshHumans es_ES
dc.subject.meshLectins, C-Type es_ES
dc.subject.meshLigands es_ES
dc.subject.meshLipoproteins, LDL es_ES
dc.titleCD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderComunidad de Madrid (España) es_ES
dc.contributor.funderFundación Ramón Areces es_ES
dc.contributor.funderFundación La Caixa es_ES
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España) es_ES
dc.identifier.journalCellular and molecular life sciences : CMLSes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Comunicación Intercelular en la Respuesta Inflamatoriaes_ES
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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