398 - Caveolin-1 is Critical for Lymphocyte Trafficking into Central Nervous System during Experimental Autoimmune Encephalomyelitis.

In the present study, we tested the hypothesis that caveolin-1 plays a critical role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a laboratory murine model of Multiple Sclerosis (MS). After active EAE induction, the increased caveolin-1 in serum and CNS tissues was associated with disease incidence and severity in immunized wild-type (WT) mice. After immunization, Cav-1knockout (KO) mice showed remarkable disease resistance with alleviated incidences and clinical symptoms. Cav-1 KO mice had diminished infiltration of encephalitogenic T cells into CNS parenchyma with compromised expressions of adhesion molecules ICAM-1 and VCAM-1 in the white matter of CNS tissues. Consistently, in vitro knockdown of caveolin-1 impaired the up-regulation of ICAM-1 in endothelial cells, and ameliorated trans-endothelial migration of pathogenic T H 1 and T H 17 cells. Therefore, caveolin-1 serves as an active modulator of lymphocyte trafficking into CNS and could be a therapeutic target for multiple sclerosis. [ABSTRACT FROM AUTHOR]