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

被引：37

作者：

Blanco-Dominguez, Rafael ^{[1
]}

de la Fuente, Hortensia ^{[2
,3
]}

Rodriguez, Cristina ^{[3
,4
,5
]}

Martin-Aguado, Laura ^{[1
]}

Sanchez-Diaz, Raquel ^{[1
,3
]}

Jimenez-Alejandre, Rosa ^{[1
]}

Rodriguez-Arabaolaza, Iker ^{[1
]}

Curtabbi, Andrea ^{[1
]}

Garcia-Guimaraes, Marcos M. ^{[6
]}

Vera, Alberto ^{[6
]}

Rivero, Fernando ^{[6
]}

Cuesta, Javier ^{[6
]}

Jimenez-Borreguero, Luis J. ^{[3
,6
]}

Cecconi, Alberto ^{[6
]}

Duran-Cambra, Albert ^{[7
]}

Tauron, Manel ^{[7
]}

Alonso, Judith ^{[3
,5
,8
]}

Bueno, Hector ^{[1
,3
,9
,10
,11
]}

Villalba-Orero, Maria ^{[1
,12
]}

Enriquez, Jose Antonio ^{[1
,13
]}

Robson, Simon C. ^{[14
]}

Alfonso, Fernando ^{[3
,6
]}

Sanchez-Madrid, Francisco ^{[1
,2
,3
]}

Martinez-Gonzalez, Jose ^{[3
,5
,8
]}

Martin, Pilar ^{[1
,3
]}

机构：

[1] CNIC, Vasc Pathophysiol Area, Madrid, Spain

[2] Univ Autonoma Madrid, Hosp Univ Princesa, Dept Immunol, IIS Princesa, Madrid, Spain

[3] CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain

[4] Inst Recerca Hosp Santa Creu & St Pau, Barcelona, Spain

[5] IIB St Pau, Barcelona, Spain

[6] Univ Autonoma Madrid, Hosp Univ Princesa, Dept Cardiol, IIS Princesa, Madrid, Spain

[7] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[8] CSIC, IIBB, Barcelona, Spain

[9] Hosp Univ 12 Octubre, Cardiol Dept, Madrid, Spain

[10] Inst Invest Sanitaria Hosp 12 Octubre Imas12, Madrid, Spain

[11] Univ Complutense Madrid, Fac Med, Madrid, Spain

[12] Univ Complutense Madrid, Fac Vet, Dept Med & Cirugia Anim, Madrid, Spain

[13] CIBER Fragilidad & Envejecimiento Saludable CIBER, Madrid, Spain

[14] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Transplantat Res Ctr, Dept Med, Boston, MA USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2022年 / 132卷 / 21期

关键词：

ST-SEGMENT ELEVATION; HEART-FAILURE; ACTIVATION; CD39; DIFFERENTIATION; QUANTIFICATION; MECHANISMS; APOPTOSIS; SOCIETY; INJURY;

D O I：

10.1172/JCI152418

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Increasing evidence has pointed to the 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 significant CD69 overexpression on Tregs after MI. Our results in mice showed that CD69 expression on Tregs increased survival after left anterior descending (LAD) coronary artery ligation. Cd69-/- mice developed strong IL-17+ gamma 8T cell responses after ischemia that increased myocardial inflammation and, consequently, worsened cardiac function. CD69+ Tregs, by induction of AhR-dependent CD39 ectonucleotidase activity, induced apoptosis and decreased IL-17A production in gamma 8T cells. Adoptive transfer of CD69+ Tregs into Cd69-/- mice after LAD ligation reduced IL-17+ gamma 8T cell recruitment, thus increasing survival. Consistently, clinical data from 2 independent cohorts of patients indicated that increased CD69 expression in peripheral blood cells after acute MI was associated with a lower risk of rehospitalization 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 Tregs as a potential prognostic factor and a therapeutic option to prevent HF after MI.

引用

页数：18

共 59 条

[1] CD69 Suppresses Sphingosine 1-Phosophate Receptor-1 (S1P1) Function through Interaction with Membrane Helix 4 [J].