Inflammation amplifier and gateway reflex: The regulation of inflammation by neuroimmune interaction

Abstract

  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.