Gateway reflex: neural activation-mediated immune cell gateways in the central nervous system

Abstract

The neural regulation of organs can be categorized as systemic or local. Whereas systemic regulation by the hypothalamus-pituitary-adrenal gland-mediated release of steroid hormones has been well studied, the mechanisms for local regulation have only recently emerged. Two types of local neural regulation are known, the gateway reflex and the inflammatory reflex. The gateway reflex describes a mechanism that converts regional neural stimulations into inflammatory outputs by changing the state of specific blood vessels. Molecularly, the enhancement of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity in endothelial cells by neurotransmitters, such as noradrenaline and ATP, induces an enhanced production of pro-inflammatory mediators, including chemokines, which form immune cell gateways at specific vessels. Several types of gateway reflex have been identified, and each regulates distinct organs by creating gateways for autoreactive T cells that induce local inflammation. On the other hand, the inflammatory reflex elicits an anti-inflammatory response through vagal nerves. Here, we summarize recent works on these two local neuro-immune interactions, giving special focus to the gateway reflex.