The role of the intracellular complement system - the complosome - in monocytes

我们的实验室已经确定了细胞内补体活性在调节人类T细胞反应中的新作用。通过与NIH和国际合作者的合作，我们现在已经扩展了这一发现，并确定了细胞内C5 ar 1在正常人类和小鼠单核细胞生物学中的作用。线粒体上的细胞内C5 aR 1信号传导是感染期间以及无菌炎症期间最佳IL-1 β产生所必需的。我们使用适当的感染（念珠菌）和CVD小鼠模型评估了这一观察结果的体内生物学意义，并注意到巨噬细胞中的细胞内C5 aR 1活性有助于小鼠和人类的CVD（正在审查的手稿）。我们目前还在测试细胞渗透性C3抑制剂在体外的作用，着眼于临床前模型的发展。

Our laboratory has identified a novel role for intracellular complement activity in the regulation of human T cell responses. In collaboration with groups from within the NIH and international collaborators, we have now extended this finding and defined a role for the intracellular C5ar1 also in normal human and mouse monocyte biology. Intracellular C5aR1 signaling on mitochondria is required for optimal IL-1beta production during infection but also sterile inflammation. We have assessed the in vivo biological significance of this observation using appropriate infection (candida) and CVD mouse models and noted that intracellular C5aR1 activity in macrophages contributes to CVD in mice and humans (manuscript under review). We are also testing currently the effects of cell-permeable C3 inhibitors in vitro with an eye on the development of preclinical models.