Dendritic cell-induced autoimmune heart failure requires cooperation between adaptive and innate immunity
Dendritic cell-induced autoimmune heart failure requires cooperation between adaptive and innate immunity
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DOI：
10.1038/nm960
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发表时间：
2003-12-01
期刊：
影响因子：
82.9
通讯作者：
Penninger, JM
中科院分区：
文献类型：
--
作者：
Eriksson, U;Ricci, R;Penninger, JM
由微生物感染引发的遗传易感性和自身免疫性是与扩张型心肌病发病机制有关的因素，扩张型心肌病是年轻患者心力衰竭的最常见原因。在这里，我们表明负载心脏特异性自身肽的树突状细胞（DC）诱导非转基因小鼠的CD4+ T细胞介导的心肌炎。Toll样受体（TLR）刺激与自身肽负载的树突细胞的CD40触发一致，显示是疾病诱导所需的。在急性心肌炎消退后，DC免疫的小鼠发展为心力衰竭，并且这些小鼠的TLR刺激导致炎性浸润复发。如果TLR在体内被激活，注射受损的同源心肌细胞也会诱导小鼠心肌炎。DC诱导的心肌炎提供了一个统一的理论，关于感染期间组织损伤和TLR活化如何诱导自身免疫、复发和心肌病。
Genetic susceptibility and autoimmunity triggered by microbial infections are factors implicated in the pathogenesis of dilated cardiomyopathy, the most common cause of heart failure in young patients. Here we show that dendritic cells (DCs) loaded with a heart- specific self peptide induce CD4+ T- cell- mediated myocarditis in nontransgenic mice. Toll- like receptor (TLR) stimulation, in concert with CD40 triggering of self peptide- loaded dendritic cells, was shown to be required for disease induction. After resolution of acute myocarditis, DC- immunized mice developed heart failure, and TLR stimulation of these mice resulted in relapse of inflammatory infiltrates. Injection of damaged, syngeneic cardiomyocytes also induced myocarditis in mice if TLRs were activated in vivo. DC- induced myocarditis provides a unifying theory as to how tissue damage and activation of TLRs during infection can induce autoimmunity, relapses and cardiomyopathy.