[Aberrant cross talk between immune cells and neural cells in demyelinating disorders]

The immune and nervous systems have similar functional characteristics. Both have an intricate network of synaptic connections and an exquisite communication system that enable to maintain homeostasis. Although semaphorins were originally identified as guidance cues in neural development, several semaphorins such as Sema4A and 4D are involved in various phases of the immune response by regulating immune cell-cell contacts, immune cell migration and immune cell-neural cell interaction. Inappropriate expression of Sema4A, 4D, and their receptors Plexin-Bs by undetermined mechanisms causes neuroinflammation that leads to demyelination. The pathogenic role of the anti-AQP4 antibody in NMO has been speculated based on studies in vitro. The fact that passive transferred IgG collected from NMO patients who underwent therapeutic plasmapheresis exacerbated EAE indicates the pathogenicity in vivo. When the antibody once penetrates the blood-brain barrier probably under an inflammatory condition primarily causes complement-dependent astrocyte damage.