William Harvey Research Institute, London, UK.
Barts and The London School of Medicine, London, UK.
Br J Pharmacol. 2017 Nov;174(22):3914-3925. doi: 10.1111/bph.13613. Epub 2016 Oct 4.
T-cell-mediated immunity has been linked not only to a variety of heart diseases, including classic inflammatory diseases such as myocarditis and post-myocardial infarction (Dressler's) syndrome, but also to conditions without an obvious inflammatory component such as idiopathic dilated cardiomyopathy and hypertensive cardiomyopathy. It has been recently proposed that in all these conditions, the heart becomes the focus of T-cell-mediated autoimmune inflammation following ischaemic or infectious injury. For example, in acute myocarditis, an inflammatory disease of heart muscle, T-cell responses are thought to arise as a consequence of a viral infection. In a number of patients, persistent T-cell-mediated responses in acute viral myocarditis can lead to autoimmunity and chronic cardiac inflammation resulting in dilated cardiomyopathy. In spite of the major progress made in understanding the mechanisms of pathogenic T-cell responses, effective and safe therapeutic targeting of the immune system in chronic inflammatory diseases of the heart has not yet been developed due to the lack of specific diagnostic and prognostic biomarkers at an early stage. This has also prevented the identification of targets for patient-tailored immunomodulatory therapies that are both disease- and organ-selective. In this review, we discuss current knowledge of the development and functional characteristics of pathogenic T-cell-mediated immune responses in the heart, and, in particular, in myocarditis, as well as recent advances in experimental models which have the potential to translate into heart-selective immunomodulation.
This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.
T 细胞介导的免疫不仅与多种心脏病有关,包括经典炎症性疾病,如心肌炎和心肌梗死后(Dressler 综合征),还与无明显炎症成分的疾病有关,如特发性扩张型心肌病和高血压性心肌病。最近有人提出,在所有这些情况下,心脏在缺血或感染损伤后成为 T 细胞介导的自身免疫炎症的焦点。例如,在急性心肌炎中,一种心肌炎症性疾病,T 细胞反应被认为是病毒感染的结果。在许多患者中,急性病毒性心肌炎中持续的 T 细胞介导的反应可导致自身免疫和慢性心脏炎症导致扩张型心肌病。尽管在理解致病性 T 细胞反应的机制方面取得了重大进展,但由于缺乏早期特定的诊断和预后生物标志物,尚未开发出针对慢性炎症性心脏病的免疫系统的有效和安全的靶向治疗方法。这也阻止了针对患者定制的免疫调节治疗的目标的鉴定,这些治疗方法既具有疾病特异性,又具有器官选择性。在这篇综述中,我们讨论了目前关于心脏中致病性 T 细胞介导的免疫反应的发展和功能特征的知识,特别是在心肌炎中,以及在实验模型方面的最新进展,这些进展有可能转化为心脏选择性免疫调节。
本文是靶向炎症以降低心血管疾病风险的专题的一部分。要查看该部分中的其他文章,请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc 和 http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc。