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Tissue-specific inflammatory diseases are regulated by several mechanisms. The gateway reflex and IL−6 amplifier are two mechanisms involved in diseases that depend on the inflammatory cytokine IL−6. The gateway reflex activates specific neural pathways that cause autoreactive CD4+ T cells to pass through gateways in blood vessels toward specific tissues in tissue-specific inflammatory diseases. These gateways are mediated by the IL−6 amplifier, which describes enhanced NF-κB activation in nonimmune cells including endothelial cells at specific sites. In total, we have reported six gateway reflexes defined by their triggering stimulus: gravity, pain, electric stimulation, stress, light, and joint inflammation. This review summarizes the gateway reflex and IL−6 amplifier for the development of tissue-specific inflammatory diseases. We expect that the IL−6 amplifier and gateway reflex will lead to novel therapeutic and diagnostic methods for inflammatory diseases, particularly tissue-specific ones.

Gateway reflexes are neural circuits that establish the gateway of immune cells to regulate tissue specific inflammation