Blanco-Domínguez, Rafaelde la Fuente, HortensiaRodríguez, CristinaMartín-Aguado, LauraSánchez-Díaz, RaquelJiménez-Alejandre, RosaRodriguez-Arabaolaza, IkerCurtabbi, AndreaGarcia-Guimaraes, Marcos MVera, AlbertoRivero, FernandoCuesta, JavierJimenez-Borreguero, Luis JesusCecconi, AlbertoDuran-Cambra, AlbertTaurón, ManelAlonso, JudithBueno, HectorVillalba-Orero, MaríaEnriquez, Jose AntonioRobson, Simon CAlfonso, FernandoSánchez-Madrid, FranciscoMartínez-González, JoséMartin, PilarGarcia-Guimaraes, Marcos M.Robson, Simon C.2022-10-312022-10-312022-09-06J Clin Invest . 2022 Sep 6;e152418.http://hdl.handle.net/20.500.12105/15107Increasing evidences advocate for an important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the underlying molecular mechanisms remain elusive. In this study, a broad analysis of immune markers in 283 patients revealed a significant CD69 overexpression on Treg cells after MI. Our results in mice showed that CD69 expression on Treg cells increased survival after left-anterior-descending coronary artery (LAD)-ligation. Cd69-/- mice developed strong IL-17+ γδT cell responses after ischemia that increased myocardial inflammation and, consequently, worsened cardiac function. CD69+ Treg cells, by induction of AhR-dependent CD39 ectonucleotidase activity, induced apoptosis and decreased IL-17A production in γδT cells. Adoptive transfer of CD69+ Treg cells to Cd69-/- mice after LAD-ligation reduced IL-17+ γδT cell recruitment, thus increasing survival. Consistently, clinical data from two independent cohorts of patients indicated that increased CD69 expression in peripheral blood cells after acute MI was associated with a lower risk of re-hospitalization for heart failure (HF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex and traditional cardiac damage biomarkers. Our data highlight CD69 expression on Treg cells as a potential prognostic factor and a therapeutic option to prevent HF after MI.engVoRhttp://creativecommons.org/licenses/by/4.0/Atribución 4.0 Internacional3606699310.1172/JCI1524181558-8238The Journal of clinical investigationopen access