Immune cell gateways in the central nervous system regulated by regional neural stimulations

Abstract

The central nervous system (CNS) is an immune-privileged tissue due to a specialized blood vessel structure, the blood-brain barrier. Indeed, the blood-brain barrier tightly limits cell migrations into the CNS. However, several immune cells, including T cells, can be found there. It is hypothesized that these cells have both beneficial and detrimental roles in immune surveillance and inflammation development, and that they can lead to multiple diseases, such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. The presence of immune cells within the CNS suggests a gateway that allows access from the peripheral blood stream. We recently identified dorsal vessels of the fifth lumbar spinal cord as a gateway for autoreactive T cells that opened with excessive chemokine expression. A chemokine inducer, the inflammation amplifier, which is hyperactivated by regional neural activations such as gravity, appears critical for formation of this fifth lumbar gateway. The gating of immune cells to the CNS can be artificially controlled by electric stimulations, at least in mice. We named this neural stimulation-dependent gating the "gateway reflex." Physical and/or chemical manipulations of the gateway reflex through the inflammation amplifier hold promising therapeutic value for neuroimmunological disorders.