The role of microglia in neuromyelitis optica

视神经脊髓炎(NMO)是一种严重的、复发性免疫球蛋白介导的自身免疫性疾病，以 中枢神经系统(CNS)，诱导炎症和优先脱髓鞘的视神经和 脊髓。大多数患者都经历了严重的损伤。星形细胞瘤特异性免疫球蛋白自身抗体 水通道蛋白-4(Aquaporin-4，AQP4)是本病的主要病理生理原因。然而， 目前对免疫球蛋白结合后导致NMO病变进展的机制知之甚少 星形胶质细胞膜进入中枢神经系统。我们提议的项目将调查潜在的 中枢神经系统的常驻免疫细胞小胶质细胞在NMO病变演变中的作用。我们有 开发了一种提供信息的NMO小鼠模型。鞘内输注NMO-Ig G。我们的预赛 结果显示明显的运动功能障碍，星形胶质细胞激活，以及早期小胶质细胞的独特模式 汇聚在星形胶质细胞上。预防小胶质细胞活动抑制运动发育 功能障碍。总之，这些数据清楚地表明星形胶质细胞-小胶质细胞的通讯是早期事件 NMO-Ig G进入中枢神经系统后。 目标1，将研究星形胶质细胞-小胶质细胞串扰的机制；目标2，将评估 小胶质细胞在NMO发病机制中的作用，Aim 3将利用新的遗传工具进行操作 小胶质细胞活性作为NMO治疗的潜在治疗方法。 我们提出的这项研究是研究小胶质细胞的具体作用的第一次尝试。 对NMO发病机制的影响。这一结果应该澄清星形胶质细胞-小胶质细胞串扰的重要性及其 NMO中的潜在机制。这项研究不仅将提高对神经免疫的理解 NMO中的相互作用，但可能会确定小胶质细胞是NMO治疗的相关靶点。

Neuromyelitis optica (NMO) is a severe, relapsing IgG-mediated autoimmune disease targeting the central nervous system (CNS), inducing inflammation and preferential demyelination of optic nerve and spinal cord. Most patients experience severe impairments. IgG autoantibodies specific for the astrocytic aquaporin-4 (AQP4) water channel are the primary cause of the disease pathophysiology. However, little is known about the mechanisms driving NMO lesion progression following the binding of IgG to the astrocyte membrane on entering the CNS. Our proposed project will investigate the potential contribution of microglia, the resident immune cell of the CNS, to the evolving NMO lesion. We have developed an informative mouse model of NMO. NMO-IgG is infused intrathecally. Our preliminary results show significant motor dysfunction, astrocyte activation, and a unique pattern of early microglial convergence on astrocytes. Prevention of microglial activity suppressed development of motor dysfunction. In sum, these data clearly indicate astrocyte-microglia communication as an early event after NMO-IgG enters the CNS. Aim 1, will investigate the mechanisms underlying astrocyte-microglia crosstalk; Aim 2, will assess the contribution of microglia to NMO pathogenesis, and Aim 3 will utilize novel genetic tools to manipulate microglial activity as a potential therapeutic approach to NMO management. The research we propose represents the first attempt to investigate the specific contribution of microglia to NMO pathogenesis. The results should clarify the importance of astrocyte-microglia crosstalk and its underlying mechanisms in NMO. The study will not only improve understanding of neuroimmune interaction in NMO but will potentially establish that microglia are a pertinent target for NMO therapy.