HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses Th17-cell expansion
HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses Th17-cell expansion
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HMGB1 阻断可减轻实验性自身免疫性心肌炎并抑制 Th17 细胞扩增
DOI：
10.1002/eji.201141879
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发表时间：
2011-12-01
影响因子：
5.4
通讯作者：
Xu, Huaxi
中科院分区：
文献类型：
--
作者：
Su, Zhaoliang;Sun, Caixia;Xu, Huaxi
高迁移率族蛋白1（HMGB 1）是一种非组蛋白核蛋白，与心血管疾病有关。扩张型心肌病（DCM）是心力衰竭的主要原因之一，通常由柯萨奇病毒B3引发的心肌炎引起，并由感染后自身免疫过程促进。Th 17细胞是一种新的CD 4（+）T细胞亚群，可能在自身免疫性心肌炎的发病机制中起重要作用。在本研究中，我们尝试用HMGB 1 B box特异性单克隆抗体阻断HMGB 1的功能，并研究阻断对Th 17细胞和实验性自身免疫性心肌炎（EAM）的影响。诱导EAM后，心脏和血液中的HMGB 1蛋白水平显著升高。给予抗HMGB 1 B box mAb可减轻心脏病理变化，并减少EAM期间心脏中浸润炎性细胞的数量。HMGB 1阻断的这些保护作用与局部组织中Th 17细胞数量减少和血清中IL-17水平降低相关。此外，体外研究表明，HMGB 1促进Th 17细胞扩增。因此，我们推测HMGB 1阻断剂通过抑制Th 17细胞来改善EAM的心脏病理变化。
High-mobility group box 1 (HMGB1), a non-histone nuclear protein, has been implicated in cardiovascular diseases. Dilated cardiomyopathy (DCM), one of the leading causes of heart failure, is often caused by coxsackievirus B3-triggered myocarditis and promoted by the post-infectious autoimmune process. Th17 cells, a novel CD4(+) T subset, may be important in the pathogenesis of autoimmune myocarditis. In the present study, we attempted to block HMGB1 function with a monoclonal antibody specific for HMGB1 B box and investigated the effects of the blockade on Th17 cells and experimental autoimmune myocarditis (EAM). After induction of EAM, HMGB1 protein levels were significantly elevated both in the heart and blood. Administration of an anti-HMGB1 B box mAb attenuated cardiac pathological changes and reduced the number of infiltrating inflammatory cells in the heart during EAM. These protective effects of HMGB1 blockade correlated with a reduced number of Th17 cells in local tissues and lower levels of IL-17 in the serum. Furthermore, in vitro, studies demonstrated that HMGB1 promoted Th17-cell expansion. Therefore, we speculate that HMGB1 blockade ameliorates cardiac pathological changes in EAM by suppressing Th17 cells.