Capture, crawl, cross: the T cell code to breach the blood–brain barriers

The central nervous system (CNS) is an immunologically privileged site to which access of circulating immune cells is tightly controlled by the endothelial blood–brain barrier (BBB; see Glossary) localized in CNS microvessels, and the epithelial blood–cerebrospinal fluid barrier (BCSFB) within the choroid plexus. As a result of the specialized structure of the CNS barriers, immune cell entry into the CNS parenchyma involves two differently regulated steps: migration of immune cells across the BBB or BCSFB into the cerebrospinal fluid (CSF)-drained spaces of the CNS, followed by progression across the glia limitans into the CNS parenchyma. With a focus on multiple sclerosis (MS) and its animal models, this review summarizes the distinct molecular mechanisms required for immune cell migration across the different CNS barriers. The central nervous system (CNS) is an immunologically privileged site to which access of circulating immune cells is tightly controlled by the endothelial blood–brain barrier (BBB; see Glossary) localized in CNS microvessels, and the epithelial blood–cerebrospinal fluid barrier (BCSFB) within the choroid plexus. As a result of the specialized structure of the CNS barriers, immune cell entry into the CNS parenchyma involves two differently regulated steps: migration of immune cells across the BBB or BCSFB into the cerebrospinal fluid (CSF)-drained spaces of the CNS, followed by progression across the glia limitans into the CNS parenchyma. With a focus on multiple sclerosis (MS) and its animal models, this review summarizes the distinct molecular mechanisms required for immune cell migration across the different CNS barriers. a subtype of ectodermal derived glial cells in the CNS characterized by many foot-like processes interacting with neurons and embracing the abluminal aspect of CNS microvessels. a diffusion barrier formed by the unique cellular and molecular characteristics of endothelial cells and the glia limitans perivascularis of the microvessels in the CNS parenchyma. At the level of CNS capillaries, the BBB forms a direct barrier. a diffusion barrier formed by the epithelial cells of the choroid plexus localized in the ventricles of the brain. a diffusion barrier formed by the unique cellular and molecular characteristics of endothelial cells of the leptomeningeal microvessels at the surface of the brain and spinal cord. Strictly speaking, the BLMB forms a blood–CSF barrier. a highly vascularized and branched villous structure developing as a protuberance from the ependymal cells lining the brain ventricles. On the outside, the choroid plexus is lined by epithelial cells involved in the production of CSF. a sieve like structure within the ethmoid bone which separates the nasal cavity from the skull cavity. composed of the parenchymal basement membrane and astrocyte foot processes and covers the entire surface of the brain and spinal cord on external surfaces towards the leptomeningeal/subarachnoid space (glia limitans superficialis) and internally towards the perivascular spaces (glia limitans perivascularis). CSF-drained space at the surface of the CNS that protects and cushions the brain and spinal cord. This space is bordered on the outside by the arachnoid mater and towards the CNS parenchyma by the pia mater. Blood vessels at the surface of the CNS are localized in this space. migration of cells in between endothelial or epithelial cells including transient opening of their cellular junctions. vascular mural cell embedded within the endothelial basement membrane of blood microvessels. migration of cells through endothelial or epithelial cells forming a pore through the cell body.