Updating Neuroimmune Targets in Central Nervous System Dysfunction

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. 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. 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. a selectively permeable barrier created by tight junctions between endothelial cells of capillaries that separates circulating blood from the brain. Provides protection for the CNS and maintains normal chemical composition necessary for normal function of the brain and its components. involved in immunoregulatory and inflammatory processes, such as inhibiting hemopoiesis and stimulating chemotaxis. Chemotactic factor for T cells, but not B cells, macrophages, or neutrophils. an epithelial–endothelial vascular system within the brain ventricles. Mainly responsible for secreting cerebral spinal fluid and also comprises part of the barrier between blood, CSF, and CNS interstitial space. fluid made by the choroid plexus that circulates in the CNS, providing buoyancy and protection for the brain, and aiding in the recycling of CNS waste products. tyrosine-protein kinase important for regulation of survival, proliferation, and differentiation of hematopoietic precursors, particularly phagocytes such as macrophages and monocytes. protein that is cleaved and secreted to act as a regulator of lysosomal function as well as a growth factor involved in inflammation, wound healing, and cell proliferation. cells (derived from skin or blood) that have been reprogrammed to a pluripotent state, enabling differentiation into a desired type of cell. Can be used for drug development research, modeling and/or treating diseases, or cell-replacement therapies. a group of rare, metabolic, genetic diseases that affect the brain, spinal cord, and often peripheral nerves. encodes a type I integral membrane glycoprotein found on lymphatic vessels. It is a ligand-specific transporter trafficking between intracellular organelles and the plasma membrane. three thin layers of tissue (named the dura, arachnoid, and pia) that cover and protect the brain and spinal cord, and enclose the CSF. In residence for CNS associated immune cells needed to support proper brain function. protein found on outermost surface of myelin sheaths and often used for modeling multiple sclerosis in mice. protective sheath around neurons, made from proteins and phospholipids, that serves as an electrical insulator, allowing for fast and efficient transmission of action potentials. high-dose chemotherapy used to kill cells in the bone marrow. functional tissue of an organ. interstitial-fluid-filled space surrounding blood vessels in the brain, surrounded by the pia layer. It is also known as Virchow–Robin space. type-I integral membrane glycoprotein expressed in multiple tissues, which mediates cell migration and adhesion. It is highly expressed in placenta, lung, skeletal muscle, and brain. transcription factor of the homeobox family that is involved in cell fate determination, the development of the heart, eye lens, liver, pancreas, and lymphatic system, and other regulatory functions. junctions between two neurons, where electrical or chemical signals are transmitted. provide structural anatomy of the thymus and are critical in positive and negative selection of T cells. triggering receptor expressed on myeloid cells 2; interacts with TYRO protein tyrosine kinase binding protein (TYROBP) to trigger inflammation in injury or disease. It is expressed on microglia, macrophages, dendritic cells, and osteoclasts. “protein important in adult lymphangiogenesis, development of the vascular network, and maintenance of lymphatic endothelium. Encoded by FLT4 gene.