Work

Caveolin-1 Is Critical for Lymphocyte Trafficking into Central Nervous System during Experimental Autoimmune Encephalomyelitis

Year: 2016

Type: article

Abstract: UNLABELLED: Multiple sclerosis (MS) is a progressive autoimmune disease of the CNS with its underlying mechanisms not fully understood. In the present study, we tested the hypothesis that caveolin-1, a major membrane scaffolding protein, plays a critical role in the pathogenesis of experimental autoimmune encephalomyelitis, a laboratory murine model of MS. We found increased expression of caveolin-1 in serum and spinal cord tissues in association with disease incidence and severity in wild-type mice with active encephalomyelitis. After immunization, Cav-1 knock-out mice showed remarkable disease resistance with decreased incidence and clinical symptoms. Furthermore, Cav-1 knock-out mice had alleviated encephalitogenic T cells trafficking into the CNS with decreased expressions of adhesion molecules ICAM-1 and VCAM-1 within the lesions. In agreement with in vivo studies, in vitro knockdown of caveolin-1 compromised the upregulation of ICAM-1 in endothelial cells, leading to the amelioration of the transendothelial migration of pathogenic TH1 and TH17 cells. Together, those results indicate that caveolin-1 serves as an active modulator of CNS-directed lymphocyte trafficking and could be a therapeutic target for neuroinflammatory diseases, such as multiple sclerosis. SIGNIFICANCE STATEMENT: The hallmark feature of neuroinflammatory diseases is the massive infiltrations of encephalitogenic leukocytes into the CNS parenchyma, a process that remains largely unclear. Our study demonstrates the critical contribution of caveolin-1 to encephalomyelitis pathogenesis and CNS-directed lymphocyte trafficking by modulation of adhesion molecules ICAM-1 and VCAM-1, highlighting the pathological involvement of caveolin-1 in neuroinflammatory diseases.

Source: Journal of Neuroscience

DOI: 10.1523/jneurosci.3734-15.2016