Nakagawa Ikuma, Murakami Masaaki
Molecular Neuroimmunology, Institute for Genetic Medicine, Hokkaido University.
Nihon Rinsho Meneki Gakkai Kaishi. 2017;40(3):160-168. doi: 10.2177/jsci.40.160.
Central nervous system (CNS), which is made up of brain and spinal cord, is protected from the invasion of harmful agents, such as various pathogens, chemical products or immune cells by a special structure "Blood Brain Barrier (BBB)". BBB highly preserves the homeostasis of CNS environment. On the other hand, there are many diseases in CNS regions which is associated with infection or autoimmunity, that means there may exist the "gateway" for pathogens or immune cells to attack CNS. Until recently, the molecular mechanism of the gateway formation has not been elucidated. Through studies in the multiple sclerosis model experimental autoimmune encephalomyelitis, we have clarified the mechanism of the gateway formation, and also the locations of gateways which depend on the regional neural activation. Further more, we have also discovered a massive chemokine-inducing mechanism "inflammation amplifier" via co-activation of NF-κB pathway and STAT3 pathway. It is essential for the development of inflammation in various diseases and is a molecular basis of BBB breakdown.
中枢神经系统(CNS)由脑和脊髓组成,它通过一种特殊结构“血脑屏障(BBB)”来抵御有害因子的入侵,这些有害因子包括各种病原体、化学产物或免疫细胞。血脑屏障高度维持着中枢神经系统环境的稳态。另一方面,中枢神经系统区域存在许多与感染或自身免疫相关的疾病,这意味着可能存在病原体或免疫细胞攻击中枢神经系统的“通道”。直到最近,通道形成的分子机制仍未阐明。通过对多发性硬化症模型实验性自身免疫性脑脊髓炎的研究,我们阐明了通道形成的机制,以及依赖于区域神经激活的通道位置。此外,我们还通过核因子κB(NF-κB)途径和信号转导子与转录激活子3(STAT3)途径的共同激活,发现了一种大量趋化因子诱导机制“炎症放大器”。它对各种疾病炎症的发展至关重要,是血脑屏障破坏的分子基础。