CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes
Entity
UAM. Departamento de MedicinaPublisher
SpringerDate
2022-08-05Citation
10.1007/s00018-022-04481-1
Cellular and Molecular Life Sciences 79 (2022): 468
ISSN
1420-682X (print); 1420-9071 (online)DOI
10.1007/s00018-022-04481-1Funded by
Open 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). Data availability The data underlying this article are available in the article and in its online Supplementary material. Declarations Conflict of interest The authors have no confict of interest to declare. Ethical approval Written consent was obtained from all participating subjects. The procedure was approved by the Ethics Committee of the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) and was conducted in accordance with the Declaration of Helsinki. Consent for publication Consent to publish has been received from all participantsProject
Gobierno de España. PDC2021-121719-I00; Gobierno de España. PDI-2020-120412RB-100; Gobierno de España. RTI2018-094727-B-100Editor's Version
https://doi.org/10.1007/s00018-022-04481-1Subjects
Anti-inflammatory response; Cardiovascular disease; CD69 leucocyte activation receptor; Inflamed aorta; oxLDL; Programmed Death 1 (PD-1); MedicinaRights
© The Author(s) 2022Abstract
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
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Google Scholar:Jiménez Fernández, María
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Rodríguez Sinovas, Cristina
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Cañes, Laia
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Ballester Servera, Carme
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Vara, Alicia
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Requena, Silvia
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de la Fuente, Hortensia
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Martínez González, José
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Sánchez Madrid, Francisco
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