Updating Neuroimmune Targets in Central Nervous System Dysfunction

• Published in: Trends in pharmacological sciences (Regular ed.) 2019-07, Vol.40 (7), p.482-494
• Main Authors: Valente, L.A., Begg, L.R., Filiano, A.J.
• Format: Article
• Language: English
• Subjects: brain engrafting macrophages; central nervous system; lymphatics; meninges; microglia; neuroimmunology
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2019.04.013

Disorders of the central nervous system (CNS) have many etiologies compounded by limited options for treatment. The lack of successful treatments for these disorders stems from the difficulty of gaining effective access to the CNS through the blood–brain barrier, and the irreplaceable nature of neurons. Here, we review recent advances in the field of neuroimmunology and discuss novel strategies for targeting microglia, meningeal lymphatics, and the peripheral immune system that may lead to successful treatment of a broad range of CNS disorders. In the future, it will be important to continue to explore the vast communications between the CNS and the immune system to map out dysfunctions that attribute to diseases such as chronic neuroinflammation, autoimmunity, CNS injury, and more. The conception of CNS immune privilege has been redefined with discovery of the meningeal lymphatic system.Meningeal lymphatics offer a conduit between the CNS and periphery, with implications in neurological dysfunction seen in AD, aging, and multiple sclerosis.Under defined conditions, hematopoietic-derived macrophages can replace CNS-resident microglia in the long term, demonstrating their feasibility as a cell-therapy approach.Manipulating peripheral immune cells with novel approaches can target neuroimmune interactions without the complications of penetrating the CNS.