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标题：P2×7 purinergic signaling in dilated cardiomyopathy induced by auto-immunity against muscarinic M₂ receptors: autoantibody levels, heart functionality and cytokine expression
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作者：Camila Guerra Martinez ; Daniel Zamith-Miranda ; Marcia Gracindo da Silva 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep16940
出版社：Springer Nature
摘要：Autoantibodies against the M₂ receptors (M₂AChR) have been associated with Dilated Cardiomyopathy (DCM). In the heart, P2×7 receptors influence electrical conduction, coronary circulation and response to ischemia. They can also trigger pro-inflammatory responses and the development of neurological, cardiac and renal disorders. Here, P2×7^−/− mice displayed an increased heart rate and ST segment depression, but similar exercise performance when compared to wild type (WT) animals. After immunization with plasmid containing M₂AChR cDNA sequence, WT mice produced anti-M₂AChR antibodies, while P2×7^−/− mice showed an attenuated production. Despite this, WT and P2×7^−/− showed left ventricle cavity enlargement and decreased exercise tolerance. Transfer of serum from M₂AChR WT immunized mice to näive recipients led to an alteration in heart shape. P2×7^−/− mice displayed a significant increase in the frequency of spleen regulatory T cells population, which is mainly composed by the FoxP3⁺CD25⁻ subset. M₂AChR WT immunized mice showed an increase in IL-1β, IFNγ and IL-17 levels in the heart, while P2×7^−/− group produced lower amounts of IL-1β and IL-17 and higher amounts of IFNγ. These results pointed to previously unnoticed roles of P2×7 in cardiovascular and immune systems, and underscored the participation of IL-17 and IFNγ in the progress of autoimmune DCM.