Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice.
Dilated cardiomyopathy is a severe pathology of the heart with poorly understood etiology. Disruption of the gene encoding the negative immunoregulatory receptor PD-1 in BALB/c mice, but not in BALB/c RAG-2-/- mice, caused dilated cardiomyopathy with severely impaired contraction and sudden death by congestive heart failure. Affected hearts showed diffuse deposition of immunoglobulin G (IgG) on the surface of cardiomyocytes. All of the affected PD-1-/- mice exhibited high-titer circulating IgG autoantibodies reactive to a 33-kilodalton protein expressed specifically on the surface of cardiomyocytes. These results indicate that PD-1 may be an important factor contributing to the prevention of autoimmune diseases.
Nishimura
H
H
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo, Kyoto, 606-8501, Japan.
Okazaki
T
T
Tanaka
Y
Y
Nakatani
K
K
Hara
M
M
Matsumori
A
A
Sasayama
S
S
Mizoguchi
A
A
Hiai
H
H
Minato
N
N
Honjo
T
T
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D003176:Complement C3 / Q000032:analysis; D004452:Echocardiography; D006333:Heart Failure / Q000209:etiology; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor
D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D001323:Autoantibodies; D001324:Autoantigens; D003176:Complement C3; D007074:Immunoglobulin G; D008565:Membrane Proteins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor