CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4+T lymphocytes
Por:
Jimenez-Fernandez, M, Rodriguez-Sinovas, C, Canes, L, Ballester-Servera, C, Vara, A, Requena, S, de la Fuente, H, Martinez-Gonzalez, J, Sanchez-Madrid, F
Publicada:
1 ago 2022
Resumen:
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.
Filiaciones:
Jimenez-Fernandez, M:
Univ Autonoma Madrid UAM, Hosp Univ la Princesa, Inst Invest Sanitaria, Hosp Univ La Princesa IIS IP, C Diego de Leon 62, Madrid 28006, Spain
Ctr Nacl Invest Cardiovasc CNIC, Madrid, Spain
Rodriguez-Sinovas, C:
Inst Recerca Hosp Santa Creu & St Pau IRHSCSP, IIB St Pau, Barcelona, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Canes, L:
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Consejo Super Invest Cient IIBB CSIC, Inst Invest Biomed Barcelona, C Rossello 161, Barcelona 08036, Spain
Ballester-Servera, C:
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Consejo Super Invest Cient IIBB CSIC, Inst Invest Biomed Barcelona, C Rossello 161, Barcelona 08036, Spain
Vara, A:
Univ Autonoma Madrid UAM, Hosp Univ la Princesa, Inst Invest Sanitaria, Hosp Univ La Princesa IIS IP, C Diego de Leon 62, Madrid 28006, Spain
Requena, S:
Univ Autonoma Madrid UAM, Hosp Univ la Princesa, Inst Invest Sanitaria, Hosp Univ La Princesa IIS IP, C Diego de Leon 62, Madrid 28006, Spain
de la Fuente, H:
Univ Autonoma Madrid UAM, Hosp Univ la Princesa, Inst Invest Sanitaria, Hosp Univ La Princesa IIS IP, C Diego de Leon 62, Madrid 28006, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Martinez-Gonzalez, J:
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Consejo Super Invest Cient IIBB CSIC, Inst Invest Biomed Barcelona, C Rossello 161, Barcelona 08036, Spain
Sanchez-Madrid, F:
Univ Autonoma Madrid UAM, Hosp Univ la Princesa, Inst Invest Sanitaria, Hosp Univ La Princesa IIS IP, C Diego de Leon 62, Madrid 28006, Spain
Ctr Nacl Invest Cardiovasc CNIC, Madrid, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Green Published, hybrid, All Open Access, Hybrid Gold, Green
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