Blockade of MCAM/CD146 impedes CNS infiltration of T cells over the choroid plexus.

ABSTRACT: BACKGROUND:Very late antigen 4 (VLA-4; integrin α4β1) is critical for transmigration of T helper (TH) 1 cells into the central nervous system (CNS) under inflammatory conditions such as multiple sclerosis (MS). We have previously shown that VLA-4 and melanoma cell adhesion molecule (MCAM) are important for trans-endothelial migration of human TH17 cells in vitro and here investigate their contribution to pathogenic CNS inflammation. METHODS:Antibody blockade of VLA-4 and MCAM is assessed in murine models of CNS inflammation in conjunction with conditional ablation of α4-integrin expression in T cells. Effects of VLA-4 and MCAM blockade on lymphocyte migration are further investigated in the human system via in vitro T cell transmigration assays. RESULTS:Compared to the broad effects of VLA

SUBMITTER: Breuer J 

PROVIDER: S-EPMC6106934 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature