CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes
The 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 inflamm...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:282323 |
| Acceso en línea: | https://ddd.uab.cat/record/282323 https://dx.doi.org/urn:doi:10.1007/s00018-022-04481-1 |
| Access Level: | acceso abierto |
| Palabra clave: | CD69 leucocyte activation receptor Oxldl Cardiovascular disease Programmed Death 1 (PD-1) Antiinfammatory response Infamed aorta |
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CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytesJiménez-Fernández, MaríaRodríguez, Cristina|||0000-0002-6472-5647Cañes Esteve, Laia|||0000-0002-9579-1321Ballester-Servera, Carme|||0000-0001-7858-3064Vara, AliciaRequena, Silviade la Fuente, HortensiaMartínez-González, José|||0000-0002-3894-7166Sánchez-Madrid, Francisco|||0000-0001-5303-0762CD69 leucocyte activation receptorOxldlCardiovascular diseaseProgrammed Death 1 (PD-1)Antiinfammatory responseInfamed aortaThe 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. 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/282323https://dx.doi.org/urn:doi:10.1007/s00018-022-04481-1reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PDC2021-121719-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-120412RB-I00Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/0919Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-094727-B-100Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-00333"la Caixa" Foundation https://doi.org/10.13039/100010434 HR17-00016open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2823232026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes |
| title |
CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes |
| spellingShingle |
CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes Jiménez-Fernández, María CD69 leucocyte activation receptor Oxldl Cardiovascular disease Programmed Death 1 (PD-1) Antiinfammatory response Infamed aorta |
| title_short |
CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes |
| title_full |
CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes |
| title_fullStr |
CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes |
| title_full_unstemmed |
CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes |
| title_sort |
CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes |
| dc.creator.none.fl_str_mv |
Jiménez-Fernández, María Rodríguez, Cristina|||0000-0002-6472-5647 Cañes Esteve, Laia|||0000-0002-9579-1321 Ballester-Servera, Carme|||0000-0001-7858-3064 Vara, Alicia Requena, Silvia de la Fuente, Hortensia Martínez-González, José|||0000-0002-3894-7166 Sánchez-Madrid, Francisco|||0000-0001-5303-0762 |
| author |
Jiménez-Fernández, María |
| author_facet |
Jiménez-Fernández, María Rodríguez, Cristina|||0000-0002-6472-5647 Cañes Esteve, Laia|||0000-0002-9579-1321 Ballester-Servera, Carme|||0000-0001-7858-3064 Vara, Alicia Requena, Silvia de la Fuente, Hortensia Martínez-González, José|||0000-0002-3894-7166 Sánchez-Madrid, Francisco|||0000-0001-5303-0762 |
| author_role |
author |
| author2 |
Rodríguez, Cristina|||0000-0002-6472-5647 Cañes Esteve, Laia|||0000-0002-9579-1321 Ballester-Servera, Carme|||0000-0001-7858-3064 Vara, Alicia Requena, Silvia de la Fuente, Hortensia Martínez-González, José|||0000-0002-3894-7166 Sánchez-Madrid, Francisco|||0000-0001-5303-0762 |
| author2_role |
author author author author author author author author |
| dc.subject.none.fl_str_mv |
CD69 leucocyte activation receptor Oxldl Cardiovascular disease Programmed Death 1 (PD-1) Antiinfammatory response Infamed aorta |
| topic |
CD69 leucocyte activation receptor Oxldl Cardiovascular disease Programmed Death 1 (PD-1) Antiinfammatory response Infamed aorta |
| description |
The 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. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2 2022-01-01 2022 2022-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/282323 https://dx.doi.org/urn:doi:10.1007/s00018-022-04481-1 |
| url |
https://ddd.uab.cat/record/282323 https://dx.doi.org/urn:doi:10.1007/s00018-022-04481-1 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PDC2021-121719-I00 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-120412RB-I00 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/0919 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-094727-B-100 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-00333 "la Caixa" Foundation https://doi.org/10.13039/100010434 HR17-00016 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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