PT  - JOURNAL ARTICLE
AU  - Wu, Hao
AU  - Deng, Ruixia
AU  - Chen, Xingmiao
AU  - Wong, Waiman Connie
AU  - Chen, Hansen
AU  - Gao, Lei
AU  - Nie, Yichu
AU  - Wu, Wutian
AU  - Shen, Jiangang
TI  - Caveolin-1 Is Critical for Lymphocyte Trafficking into Central Nervous System during Experimental Autoimmune Encephalomyelitis
AID  - 10.1523/JNEUROSCI.3734-15.2016
DP  - 2016 May 11
TA  - The Journal of Neuroscience
PG  - 5193--5199
VI  - 36
IP  - 19
4099  - http://www.jneurosci.org/content/36/19/5193.short
4100  - http://www.jneurosci.org/content/36/19/5193.full
SO  - J. Neurosci.2016 May 11; 36
AB  - 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.