The role of mitochondria in the pathogenesis of Kawasaki disease.
The role of mitochondria in the pathogenesis of Kawasaki disease.
复制标题
DOI：
10.3389/fimmu.2022.1017401
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
川崎病是一种影响儿童的系统性脉管炎，尤其是冠状动脉。尽管进行了广泛的研究，但对于放大的炎症反应背后的主要驱动因素仍有许多未知之处。我们认为线粒体可能起着关键作用。线粒体作为中心枢纽，影响能量的产生、细胞的增殖和生物能量学。然而，对这些生物过程的监管是有代价的。线粒体DNA释放到细胞质中，作为损伤相关的分子模式，启动炎症的发展。作为活性氧物种的来源，它们促进NLRP3炎症体的激活。川崎病涉及许多这样的炎症途径。进行性线粒体功能障碍改变了免疫细胞的活性，可能在川崎病的发病机制中起一定作用。由于线粒体包含自己的基因组，因此很容易发生突变，从而传播其功能障碍和免疫刺激潜力。线粒体DNA的群体特异性变异也与疾病风险和治疗反应的种族差异有关。我们的目标是批判性地审查目前关于线粒体在协调促炎信号通路中的作用的文献，重点关注川崎病中潜在的线粒体功能障碍。线粒体功能受损与川崎病之间不存在关联，但我们认为两者之间存在联系。我们假设了一个线粒体决定因素的框架，它可能导致川崎病进展过程中的种族/种族差异。
Kawasaki disease is a systemic vasculitis, especially of the coronary arteries, affecting children. Despite extensive research, much is still unknown about the principal driver behind the amplified inflammatory response. We propose mitochondria may play a critical role. Mitochondria serve as a central hub, influencing energy generation, cell proliferation, and bioenergetics. Regulation of these biological processes, however, comes at a price. Release of mitochondrial DNA into the cytoplasm acts as damage-associated molecular patterns, initiating the development of inflammation. As a source of reactive oxygen species, they facilitate activation of the NLRP3 inflammasome. Kawasaki disease involves many of these inflammatory pathways. Progressive mitochondrial dysfunction alters the activity of immune cells and may play a role in the pathogenesis of Kawasaki disease. Because they contain their own genome, mitochondria are susceptible to mutation which can propagate their dysfunction and immunostimulatory potential. Population-specific variants in mitochondrial DNA have also been linked to racial disparities in disease risk and treatment response. Our objective is to critically examine the current literature of mitochondria’s role in coordinating proinflammatory signaling pathways, focusing on potential mitochondrial dysfunction in Kawasaki disease. No association between impaired mitochondrial function and Kawasaki disease exists, but we suggest a relationship between the two. We hypothesize a framework of mitochondrial determinants that may contribute to ethnic/racial disparities in the progression of Kawasaki disease.