The osteopontin - CD44 pathway is superfluous for the development of autoimmune myocarditis.
Osteopontin (OPN) and CD44 have been implicated in the development of autoimmune diseases, including arthritis and multiple sclerosis, as well as chronic inflammatory diseases, such as atherosclerosis and colitis. To investigate their roles in autoimmune myocarditis induced by immunization with heart alpha-myosin (MyHC-alpha), a mouse model of human cardiomyopathy, we analyzed mice lacking OPN or CD44v6/v7, a CD44 isoform that binds OPN. Both, OPN(-/-) and CD44v6/v7(-/-) mice developed myocarditis with the same prevalence and severity as BALB/c wild-type controls. Furthermore, treatment of BALB/c mice with a pan-neutralizing anti-CD44 antibody did not affect the disease outcome. Consistently, expansion of MyHC-alpha-specific autoimmune CD4(+) T cells and MyHC-alpha autoantibody responses from either CD44v6/v7(-/-) mice or OPN(-/-) mice was indistinguishable from their wild-type controls. Thus, OPN and CD44v6/v7 are merely spectators rather than protagonists in autoimmune myocarditis.
Abel
Brian
B
Molecular Biomedicine, ETH Zürich, Zürich-Schlieren, Switzerland.
Kurrer
Michael
M
Shamshiev
Abdijapar
A
Marty
Rene R
RR
Eriksson
Urs
U
Günthert
Ursula
U
Kopf
Manfred
M
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009205:Myocarditis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000172:deficiency / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D024723:Ventricular Myosins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D001323:Autoantibodies; C112697:CD44v6 antigen; C476399:Cd44 protein, mouse; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D024723:Ventricular Myosins