[Gateway Reflex, a regulator of the inflammation feedback loop by regional neural activation]

Inflammation is observed in many diseases and disorders. We discovered a key machinery of inflammation, the inflammation amplifier, which is induced by the simultaneous activation of NFκB and STAT3 followed by the hyper-activation of NFκB in non-immune cells, including endothelial cells and fibroblasts. Since that discovery, we found the Gateway Reflex, which describes regional neural activations that enhance the inflammation amplifier to create a gateway for immune cells to bypass the blood-brain barrier. In addition, we have identified over 1,000 positive regulators and over 500 targets of the inflammation amplifier, which include a significant numbers of human disease-associated genes. In parallel, we performed a comprehensive analysis of human disease samples and found that the inflammation amplifier was activated during the development of chronic inflammation. Thus, we concluded that the inflammation amplifier is associated with various human diseases and disorders, including autoimmune diseases, metabolic syndromes, neurodegenerative diseases, and other inflammatory diseases. We are now attempting drug discovery for inflammatory diseases and disorders based on the inflammation amplifier and Gateway Reflex. In this review, we discuss the Gateway Reflex as an example for the neuro-immune interaction in vivo.