CD69 Limits the Severity of Cardiomyopathy After Autoimmune Myocarditis
CD69 Limits the Severity of Cardiomyopathy After Autoimmune Myocarditis
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DOI：
10.1161/circulationaha.110.952820
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发表时间：
2010-10-05
期刊：
影响因子：
37.8
通讯作者：
Martin, Pilar
中科院分区：
文献类型：
--
作者：
Cruz-Adalia, Aranzazu;Jesus Jimenez-Borreguero, Luis;Martin, Pilar
背景-实验性自身免疫性心肌炎(EAM)是感染后心肌病的小鼠模型，反映了人类炎症性心肌病的机制。EAM的特点是炎症细胞渗入心肌，继而可导致心肌细胞纤维化、水肿和坏死，导致室壁功能障碍和心力衰竭。不同的数据表明CD69在体内发挥着重要的免疫调节作用。然而，CD69在自身免疫性心肌炎中的可能作用还没有研究。方法和结果-我们探讨了白细胞调节分子CD69在EAM心肌损伤后导致心功能不全的炎症中的作用。我们发现，在EAM诱导后，CD69缺陷小鼠的引流淋巴结出现了加剧的Th17炎症反应，导致心肌中浸润性白细胞的数量增加。在EAM慢性期，经胸超声心动图显示CD69缺陷小鼠的左室短轴缩短率和射血分数显著降低，这表明心脏收缩能力受损。伴随着这种情况的是更大程度的心肌纤维化，心电图上窦性停顿的数量增加，以及CD69(-/-)小鼠的心脏重量/体重比增加。此外，骨髓移植和从免疫的EAM(-/-)小鼠分离的Th17细胞过继转移到幼稚的野生型受体中都复制了疾病的严重程度，证明CD69在淋巴细胞内发挥其功能。结论-我们的研究结果表明CD69负性调节EAM的心脏特异性Th17反应、心脏炎症和心力衰竭进展。(发行量。2010年；122：1396-1404。)
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.Methods and 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.Conclusion-Our findings indicate that CD69 negatively regulates heart-specific Th17 responses, cardiac inflammation, and heart failure progression in EAM. (Circulation. 2010;122:1396-1404.)