**8. Future directions**

The CNS is an immune‐privileged site protected by the BBB, but the gateway reflex, which can be triggered by various neural stimulations, can induce gateways for immune cells to circumvent the BBB. So far, three kinds of gateway reflex have been identified: gravity, elec‐ tric stimulation, and pain‐induced, all of which involve sensory‐sympathetic communica‐ tion. Further study of the mechanisms driving the gateway reflex should consider the neural network involved and whether it is present in other organs and tissues. Newly developed imaging techniques and tools including a tissue decolorization reagent, CUBIC [69, 70], will help elucidate the former. For the latter, it is recently reported there exists barrier architec‐ ture with similar components to the BBB in the gut endothelium, the so‐called gut‐vascular barrier [22]. A similar system may explain how immune cells breach this barrier. Because neuronal circuits run throughout the body, the gateway reflex could have a tremendous clinical benefit, as closing a specific gateway would dampen autoimmune inflammation in a target organ without massive systemic immune suppression, while opening it in tumors could enhance cancer immunotherapy.
