Fighting Chronic Neuroinflammation by Boosting Autoimmunity: The Distinction Between Neurodegenerative Diseases and Multiple Sclerosis

For decades, the brain was considered to be a tissue behind barriers, and thus autonomous with respect to its maintenance needs. Several years ago, our group suggested that the ability of the brain to operate optimally, with relatively little deterioration throughout life, is dependent on continuous support from circulating immune cells. We envisioned that such immune support is provided from specific permissive sites that lie between the brain and the immune system, enabling immune-brain dialogue without the risk of an inflammatory autoimmune response. The brain's choroid plexus has been identified as an active neuroimmunological interface that is continuously exposed to signals from the brain and from the periphery. The interplay between these bidirectional signals shapes brain function in health and disease, including in multiple sclerosis. Accumulating evidence suggests that autoimmune T cells that recognize brain antigens are involved in this dialogue. Here, we discuss the fate of this dialogue under neurodegenerative conditions, and how boosting autoimmunity, rather than suppressing it, by either active vaccination with central nervous system-derived antigens, or by breaking peripheral immune suppression, could be harnessed for mitigating neurodegenerative diseases.