Suppressor of cytokine signaling 1 DNA administration inhibits inflammatory and pathogenic responses in autoimmune myocarditis.
Myocarditis and subsequent dilated cardiomyopathy are major causes of heart failure in young adults. Myocarditis in humans is highly heterogeneous in etiology. Recent studies have indicated that a subgroup of myocarditis patients may benefit from immune-targeted therapies, because autoimmunity plays an important role in myocarditis as well as contributing to the progression to cardiomyopathy and heart failure. Suppressor of cytokine signaling (SOCS) 1 plays a key role in the negative regulation of both TLR- and cytokine receptor-mediated signaling, which is involved in innate immunity and subsequent adaptive immunity. In this study, we investigated the therapeutic effect of SOCS1 DNA administration on experimental autoimmune myocarditis (EAM) in mice. EAM was induced by s.c. immunization with cardiac-specific peptides derived from α myosin H chain in BALB/c mice. In contrast to control myocarditis mice, SOCS1 DNA-injected mice were protected from development of EAM and heart failure. SOCS1 DNA administration was effective for reducing the activation of autoreactive CD4(+) T cells by inhibition of the function of Ag-presenting dendritic cells. Our findings suggest that SOCS1 DNA administration has considerable therapeutic potential in individuals with autoimmune myocarditis and dilated cardiomyopathy.
Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843, Japan.
Kazuko
K
Tajiri
Kyoko
K
Imanaka-Yoshida
Akihiro
A
Matsubara
Yusuke
Y
Tsujimura
Michiaki
M
Hiroe
Tetsuji
T
Naka
Nobutake
N
Shimojo
Satoshi
S
Sakai
Kazutaka
K
Aonuma
Yasuhiro
Y
Yasutomi
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D004247:DNA / Q000008:administration & dosage; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D023421:Models, Animal; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D004247:DNA