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CD69 expression on regulatory T cells protects from immune damage after myocardial infarction

Rafael Blanco-Domínguez,¹ Hortensia de la Fuente,² Cristina Rodríguez,³ Laura Martín-Aguado,¹ Raquel Sánchez-Díaz,¹ Rosa Jiménez-Alejandre,¹ Iker Rodriguez-Arabaolaza,¹ Andrea Curtabbi,¹ Marcos M. Garcia-Guimaraes,⁴ Alberto Vera,⁴ Fernando Rivero,⁴ Javier Cuesta,⁴ Luis Jesus Jimenez-Borreguero,⁴ Alberto Cecconi,⁴ Albert Duran-Cambra,⁵ Manel Taurón,⁵ Judith Alonso,⁶ Héctor Bueno,⁷ María Villalba-Orero,¹ José Antonio Enriquez,¹ Simon C. Robson,⁸ Fernando Alfonso,⁴ Francisco Sánchez-Madrid,¹ José Martínez-González,⁶ and Pilar Martín¹

Published September 6, 2022 - More info

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CD69 expression protects from immune damage after MI

Video Abstracts

In this episode, Dr. Blanco-Domínguez discusses CD69 expression on regulatory T cells after myocardial infarction controls immune homeostasis and prevents death and chronic heart failure development in mice and humans.

Increasing 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.

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