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，我们现在扩展了这一发现，并确定了细胞内C5ar1在正常人类和小鼠单核细胞生物学中的作用。细胞内线粒体上的C5aR1信号是感染期间最佳il -1 β产生所必需的，也是无菌炎症所必需的。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，并注意到巨噬细胞内C5aR1活性有助于小鼠和人类的CVD（论文正在审查中）。我们目前也在体外测试细胞渗透性C3抑制剂的作用，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.