Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Sweden; Department of Cardiothoracic Surgery and Anaesthesia, Uppsala University Hospital, Sweden; Department of Surgical Sciences, Uppsala University, Sweden.
Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Sweden.
Clin Immunol. 2016 May;166-167:89-95. doi: 10.1016/j.clim.2016.04.003. Epub 2016 Apr 13.
Besides its vital role in immunity, the complement system also contributes to the shaping of the synaptic circuitry of the brain. We recently described that soluble Complement Receptor 2 (sCR2) is part of the nerve injury response in rodents. We here study CR2 in context of multiple sclerosis (MS) and explore the molecular effects of CR2 on C3 activation. Significant increases in sCR2 levels were evident in cerebrospinal fluid (CSF) from both patients with relapsing-remitting MS (n=33; 6.2ng/mL) and secondary-progressive MS (n=9; 7.0ng/mL) as compared to controls (n=18; 4.1ng/mL). Furthermore, CSF sCR2 levels correlated significantly both with CSF C3 and C1q as well as to a disease severity measure. In vitro, sCR2 inhibited the cleavage and down regulation of C3b to iC3b, suggesting that it exerts a modulatory role in complement activation downstream of C3. These results propose a novel function for CR2/sCR2 in human neuroinflammatory conditions.
除了在免疫中发挥重要作用外，补体系统还有助于大脑突触回路的形成。我们最近描述了可溶性补体受体 2 (sCR2) 是啮齿动物神经损伤反应的一部分。在这里，我们研究了 CR2 在多发性硬化症 (MS) 中的情况，并探讨了 CR2 对 C3 激活的分子影响。与对照组（n=18；4.1ng/mL）相比，复发缓解型 MS（n=33；6.2ng/mL）和继发进展型 MS（n=9；7.0ng/mL）患者的脑脊液（CSF）中 sCR2 水平明显升高。此外，CSF sCR2 水平与 CSF C3 和 C1q 以及疾病严重程度的衡量标准显著相关。体外，sCR2 抑制 C3b 至 iC3b 的裂解和下调，表明它在 C3 下游的补体激活中发挥调节作用。这些结果提出了 CR2/sCR2 在人类神经炎症中的新功能。
