Journal
JOURNAL OF NEUROSCIENCE
Volume 36, Issue 19, Pages 5193-5199Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3734-15.2016
Keywords
caveolin-1; experimental autoimmune encephalomyelitis; ICAM-1; lymphocyte trafficking; VCAM-1
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Funding
- Hong Kong Research Council Grant RGC GRF [17118511]
- University of Hong Kong Seed Fund for Basic Research [201311159015]
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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 T(H)1 and T(H)17 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.
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