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The central nervous system (CNS) is an immune‐privileged tissue protected by the brain– blood barrier (BBB), which limits the absorption of substances and cells from blood flow. In the case of inflammatory diseases in the CNS, such as multiple sclerosis (MS), however, autoreactive T cells that attack brain autoantigens, including myelin proteins, circum‐ vent the BBB. Despite the wide distribution of brain autoantigens, demyelination often occurs as discrete foci. This fact suggests that there might be a certain cue that guides autoreactive T cells to particular site(s) in the CNS. In other words, there exists a mechanism that facilitates a site‐specific accumulation of autoreactive T cells in the CNS. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we identi‐ fied dorsal vessels of the fifth lumbar (L5) spinal cord as the initial entry site of immune cells. The formation of a gateway for immune cells is defined by local neural stimula‐ tions. For example, neural stimulation by gravity creates this gateway by increasing the expression of chemokines that attract autoreactive T cells. Regional neural activation by the other stimuli, such as electric pulses or pain sensation, also induces gateway formation, but at different blood vessels via chemokine expression. These neuro‐immune interac‐ tions are examples of the gateway reflex and are extensively reviewed in this chapter.

The Gateway Reflex, a Novel Neuro‐immune Interaction, is Critical for the Development of Mouse Multiple Sclerosis (MS) Models