Institute for Immunology and School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing 100084, China.
Institute for Immunology and School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing 100084, China.
Exp Neurol. 2019 Dec;322:113056. doi: 10.1016/j.expneurol.2019.113056. Epub 2019 Sep 5.
Inflammatory response triggered by nerve injury plays important roles in the development of neurological disorders, such as neuropathic pain. The signaling events leading to inflammation in the nervous system remain poorly understood. Here, by deleting Dlk in sensory neurons driven by Wnt1a-Cre, we show that dual leucine zipper kinase (DLK) is required for the neuronal intrinsic immune response to induce cytokines and chemokines such as Ccl2, Ccl7, and Ccl12 upon nerve injury. The DLK-controlled injury response in sensory neurons could regulate CD11b immune cell infiltration in the dorsal root ganglia, as well as microgliosis and astrogliosis in the spinal dorsal horn but not the ventral horn. Deficiency of Dlk drastically alleviates the neuropathic pain elicited by chronic constriction injury of the sciatic nerve. Thus, DLK is an essential component that mediates the neuronal intrinsic immune response to nerve injury in sensory neurons and regulates inflammation in the spinal cord.
神经损伤引发的炎症反应在神经紊乱的发展中起着重要作用，如神经性疼痛。导致神经系统炎症的信号事件仍知之甚少。在这里，我们通过 Wnt1a-Cre 驱动的感觉神经元中删除 Dlk，表明双亮氨酸拉链激酶 (DLK) 是神经元内在免疫反应所必需的，以在神经损伤后诱导细胞因子和趋化因子，如 Ccl2、Ccl7 和 Ccl12。感觉神经元中由 DLK 控制的损伤反应可以调节背根神经节中的 CD11b 免疫细胞浸润，以及脊髓背角中的小胶质细胞增生和星形胶质细胞增生，但不影响腹角。Dlk 的缺失极大地减轻了坐骨神经慢性缩窄损伤引起的神经性疼痛。因此，DLK 是一种重要的组成部分，它介导感觉神经元中神经元内在免疫反应对神经损伤的反应，并调节脊髓中的炎症。
