Involvement of the choroid plexus in central nervous system inflammation

During inflammatory conditions in the central nervous system (CNS), immune cells immigrate into the CNS and can be detected in the CNS parenchyma and in the cerebrospinal fluid (CSF). The most comprehensively investigated mod el for CNS inflammation is experimental autoimmune encephalomyelitis (EAE), which is considered the prototype model for the human disease multiple scl erosis (MS). In EAE: autoagressive CD4(+), T cells gain access to the CNS a nd initiate the molecular and cellular events leading to edema, inflammatio n, and demyelination in the CNS. The endothelial blood-brain barrier (BBB) has been considered the obvious place of entry for the circulating immune c ells into the CNS. A role of the choroid plexus in the pathogenesis of EAE or MS, i.e., as an alternative entry site for circulating lymphocytes direc tly into the CSF, has not been seriously considered before. However, during EAE, we observed massive ultrastructural changes within the choroid plexus , which are different from changes observed during hypoxia. Using immunohis tochemistry and in situ hybridization, we observed expression of VCAM-1 and ICAM-1 in the choroid plexus and demonstrated their upregulation and also de novo expression of MAdCAM-1 during EAE. Ultrastructural studies revealed polar localization of ICAM-1, VCAM-1, and MAdCAM-1 on the apical surface o f choroid plexus epithelial cells and their complete absence on the fenestr ated endothelial cells within the choroid plexus parenchyme. Furthermore, I CAM-1, VCAM-1, and MAdCAM-1 expressed in choroid plexus epithelium mediated binding of lymphocytes via their known ligands. In vitro, choroid plexus e pithelial cells can be induced to express ICAM-1, VCAM-1, MAdCAM-1, and, ad ditionally, NHC class I and II molecules on their surface. Taken together, our observations imply a previously unappreciated function of the choroid p lexus in the immunosurveillance of the CNS. (C) 2001 Wiley-Liss, Inc.