Michel Nathaly Anto, Zirlik Andreas, Wolf Dennis
Faculty of Medicine, Department of Cardiology and Angiology I, Heart Center Freiburg, University of Freiburg, Freiburg, Germany.
Front Cardiovasc Med. 2017 Jun 20;4:40. doi: 10.3389/fcvm.2017.00040. eCollection 2017.
CD40L (CD154), a member of the tumor necrosis factor superfamily, is a co-stimulatory molecule that was first discovered on activated T cells. Beyond its fundamental role in adaptive immunity-ligation of CD40L to its receptor CD40 is a prerequisite for B cell activation and antibody production-evidence from more than two decades has expanded our understanding of CD40L as a powerful modulator of inflammatory pathways. Although inhibition of CD40L with neutralizing antibodies has induced life-threatening side effects in clinical trials, the discovery of cell-specific effects and novel receptors with distinct functional consequences has opened a new path for therapies that specifically target detrimental properties of CD40L. Here, we carefully evaluate the signaling network of CD40L by gene enrichment analysis and its cell-specific expression, and thoroughly discuss its role in cardiovascular pathologies with a specific emphasis on atherosclerotic and thrombotic disease.
CD40L(CD154)是肿瘤坏死因子超家族的成员,是一种共刺激分子,最初在活化的T细胞上被发现。除了在适应性免疫中的基本作用(CD40L与其受体CD40的结合是B细胞活化和抗体产生的先决条件)之外,二十多年来的证据扩展了我们对CD40L作为炎症途径强大调节剂的理解。尽管在临床试验中用中和抗体抑制CD40L会引发危及生命的副作用,但细胞特异性效应和具有不同功能后果的新型受体的发现为特异性靶向CD40L有害特性的治疗开辟了一条新途径。在这里,我们通过基因富集分析仔细评估CD40L的信号网络及其细胞特异性表达,并深入讨论其在心血管疾病中的作用,特别强调动脉粥样硬化和血栓形成性疾病。