Suppressor of Cytokine Signaling 1 DNA Administration Inhibits Inflammatory and Pathogenic Responses in Autoimmune Myocarditis
Suppressor of Cytokine Signaling 1 DNA Administration Inhibits Inflammatory and Pathogenic Responses in Autoimmune Myocarditis
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DOI：
10.4049/jimmunol.1103610
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发表时间：
2012-08-15
影响因子：
4.4
通讯作者：
Yasutomi, Yasuhiro
中科院分区：
文献类型：
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作者：
Tajiri, Kazuko;Imanaka-Yoshida, Kyoko;Yasutomi, Yasuhiro
心肌炎和随后的扩张性心肌病是年轻人心力衰竭的主要原因。人类心肌炎的病因是高度异质性的。最近的研究表明，一组心肌炎患者可能受益于免疫靶向治疗，因为自身免疫在心肌炎中起着重要作用，并有助于心肌病和心力衰竭的进展。细胞因子信号传导抑制因子1 （Suppressor of cytokine signaling， SOCS）在TLR和细胞因子受体介导的信号传导负调控中起关键作用，参与先天免疫和随后的适应性免疫。在本研究中，我们研究了SOCS1 DNA给药对小鼠实验性自身免疫性心肌炎（EAM）的治疗作用。BALB/c小鼠用肌球蛋白H链衍生的心脏特异性肽免疫sc诱导EAM。与对照组心肌炎小鼠相比，注射SOCS1 dna的小鼠免受EAM和心力衰竭的影响。通过抑制ag呈递树突状细胞的功能，SOCS1 DNA给药可以有效地降低自身反应性CD4(+) T细胞的激活。我们的研究结果表明，在自身免疫性心肌炎和扩张型心肌病患者中，给药SOCS1 DNA具有相当大的治疗潜力。中国生物医学工程学报，2012,33(2):444 - 444。
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 a 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. The Journal of Immunology, 2012, 189: 2043-2053.