Lack of Junctional Adhesion Molecule (JAM)-B ameliorates experimental autoimmune encephalomyelitis

Publication date: Available online 18 June 2018 Source:Brain, Behavior, and Immunity Author(s): Silvia Tietz, Therese Périnat, Gretchen Greene, Gaby Enzmann, Urban Deutsch, Ralf Adams, Beat Imhof, Michel Aurrand-Lions, Britta Engelhardt In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) autoaggressive CD4+ T cells cross the blood-brain barrier (BBB) and cause neuroinflammation. Therapeutic targeting of CD4+T-cell trafficking into the CNS by blocking α4-integrins has proven beneficial for the treatment of MS but comes with associated risks, probably due to blocking CD8+ T cell mediated CNS immune surveillance. Our recent observations show that CD8+ T cells also rely on α4β1 -integrins to cross the BBB. Besides vascular cell adhesion molecule-1 (VCAM-1), we identified junctional adhesion molecule -B (JAM-B) as a novel vascular α4β1 -integrin ligand involved in CD8+ T-cell migration across the BBB. This prompted us to investigate, if JAM-B also mediates CD4+ T-cell migration across the BBB. We first ensured that encephalitogenic T cells can bind to JAM-B in vitro and next compared EAE pathogenesis in JAM-B-/- C57BL/6J mice and their wild-type littermates. Following immunization with MOGaa35-55 peptide, JAM-B-/- mice developed ameliorated EAE compared to their wild-type littermates. At the same time, we isolated higher numbers of CD45+ infiltrating immune cells from the CNS of JAM-B-/- C57BL/6J mice suffering from EAE....
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research