The involvement of ICAM-5 in regulation of the immunologic synapse in brain. Dendritic cells and/or microglia are the local APCs in the brain. In the case of brain inflammation, they control the activation of invaded T cells through TCR and costimulatory molecules, such as CD28 and LFA-1. Activated T cells or microglial cells secrete MMPs, which in turn cleave the ectodomains of ICAM-5 from neurons, producing sICAM-5. sICAM-5 may compete with ICAM-1 at the early T-cell priming stage and neutralize the costimulatory signal induced by ICAM-1 for T-cell activation.