title: CD69 limits the severity of cardiomyopathy after autoimmune myocarditis.
abstract: BACKGROUND
  Experimental autoimmune myocarditis (EAM), a mouse model of post-infectious cardiomyopathy, reflects mechanisms of inflammatory cardiomyopathy in humans. EAM is characterized by an infiltration of inflammatory cells into the myocardium that can be followed by myocyte fibrosis, edema, and necrosis, leading to ventricular wall dysfunction and heart failure. Different data indicate that CD69 exerts an important immunoregulatory effect in vivo. However, the possible role of CD69 in autoimmune myocarditis has not been studied.
  
  
  RESULTS
  We have explored the role of the leukocyte regulatory molecule CD69 in the inflammation that leads to cardiac dysfunction after myocardial injury in EAM. We have found that after induction of EAM, the draining lymph nodes from CD69-deficient mice developed an exacerbated Th17 inflammatory response, resulting in increases in the numbers of infiltrating leukocytes in the myocardium. In the chronic phase of EAM, transthoracic echocardiography revealed a significantly reduced left ventricular fractional shortening and a decreased ejection fraction in CD69-deficient mice, indicative of an impaired cardiac contractility. This condition was accompanied by a greater extent of myocardial fibrosis, an elevated number of sinus pauses on ECG, and an enhanced ratio of heart weight to body weight in CD69-/- mice. Moreover, both bone marrow transplantation and adoptive transfer of Th17 cells isolated from immunized CD69-/- mice with EAM into naive wild-type recipients reproduced the severity of the disease, demonstrating that CD69 exerts its function within the lymphocyte compartment.
  
  
  CONCLUSIONS
  Our findings indicate that CD69 negatively regulates heart-specific Th17 responses, cardiac inflammation, and heart failure progression in EAM.
authors.affiliation: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernández Almagro, Madrid, Spain.
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Cruz-Adalia
authors.forename: Luis Jesús
authors.initials: LJ
authors.lastname: Jiménez-Borreguero
authors.forename: Marta
authors.initials: M
authors.lastname: Ramírez-Huesca
authors.forename: Isabel
authors.initials: I
authors.lastname: Chico-Calero
authors.forename: Olga
authors.initials: O
authors.lastname: Barreiro
authors.forename: Erica
authors.initials: E
authors.lastname: López-Conesa
authors.forename: Manuel
authors.initials: M
authors.lastname: Fresno
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: Pilar
authors.initials: P
authors.lastname: Martín
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D003433:Crosses, Genetic; D004719:Endomyocardial Fibrosis / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D037181:Lectins, C-Type / Q000172:deficiency* / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009205:Myocarditis / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology / Q000502:physiology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D018995:Myosin Heavy Chains; D010446:Peptide Fragments; D000099192:CD69 Antigens