Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Neuron. 2015 Feb 18;85(4):703-9. doi: 10.1016/j.neuron.2015.01.013. Epub 2015 Feb 5.
Inflammation is a prominent feature of CNS injury that heavily influences neuronal survival, yet the signals that initiate and control it remain poorly understood. Here we identify the nuclear alarmin, interleukin (IL)-33, as an important regulator of the innate immune response after CNS injury. IL-33 is expressed widely throughout the healthy brain and is concentrated in white mater due to predominant expression in post-mitotic oligodendrocytes. IL-33 is released immediately after CNS injury from damaged oligodendrocytes, acting on local astrocytes and microglia to induce chemokines critical for monocyte recruitment. Mice lacking IL-33 have impaired recovery after CNS injury, which is associated with reduced myeloid cell infiltrates and decreased induction of M2 genes at the injury site. These results demonstrate a novel molecular mediator contributing to immune cell recruitment to the injured CNS and may lead to new therapeutic insights in CNS injury and neurodegenerative diseases.
炎症是中枢神经系统损伤的一个显著特征，它对神经元的存活有很大影响，但引发和控制炎症的信号仍知之甚少。在这里，我们发现核警报素白细胞介素（IL）-33 是中枢神经系统损伤后固有免疫反应的重要调节剂。IL-33 在健康大脑中广泛表达，并由于在有丝分裂后少突胶质细胞中的主要表达而集中在白质中。IL-33 在中枢神经系统损伤后立即从受损的少突胶质细胞中释放出来，作用于局部星形胶质细胞和小胶质细胞，诱导对单核细胞募集至关重要的趋化因子。缺乏 IL-33 的小鼠在中枢神经系统损伤后恢复受损，这与髓样细胞浸润减少和损伤部位 M2 基因的诱导减少有关。这些结果表明了一种新的分子介导物，有助于免疫细胞募集到受损的中枢神经系统，并可能为中枢神经系统损伤和神经退行性疾病带来新的治疗思路。
