Chapters authored
The Gateway Reflex, a Novel Neuro‐immune Interaction, is Critical for the Development of Mouse Multiple Sclerosis (MS) Models
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, circumvent 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 identified 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 stimulations. 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 interactions are examples of the gateway reflex and are extensively reviewed in this chapter.
Part of the book: Trending Topics in Multiple Sclerosis
Gateway Reflex: A Neuro-Immune Crosstalk for Organ-Specific Disease Development
Homeostasis of the central nervous system (CNS) is strictly regulated by a unique structure of blood vessels, the blood-brain barrier (BBB). Experimental and clinical evidence has revealed that abnormalities in the BBB in chronic inflammatory diseases such as multiple sclerosis (MS). By using an animal model of MS, we identified novel neuro-immune crosstalk to explain how pathogenic immune cells enter the CNS to disrupt its homeostasis, a phenomenon we named the gateway reflex. Regional neural inputs such as gravity, electricity, pain or chronic stress cause specific neural activation to create a gateway of immune cells, particularly pathogenic ones, at specific blood vessels. Moreover, the recently discovered stress-induced gateway reflex uncovered a stress-induced neural link between the brain, gastrointestine, and heart. Thus, the gateway reflex is critical for the homeostasis of various organs, and aberrant activation of neural pathways by the gateway reflex disrupts normal organ homeostasis. The inflammatory reflex is another mechanism for local neuro-immune interactions. It potently exerts a cholinergic anti-inflammatory effect on various disease conditions. In this section, we discuss emerging roles for local neuro-immune interactions, with a special focus on the gateway reflex.
Part of the book: Homeostasis