title: Caveolin-1 Is Critical for Lymphocyte Trafficking into Central Nervous System during Experimental Autoimmune Encephalomyelitis.
abstract: 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.
  
  
  
  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.
authors.affiliation: School of Chinese Medicine, University of Hong Kong, Hong Kong SAR, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: School of Chinese Medicine, University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ruixia
authors.initials: R
authors.lastname: Deng
authors.affiliation: School of Chinese Medicine, University of Hong Kong, Hong Kong SAR, China.
authors.forename: Xingmiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Biomedical Science, University of Hong Kong, Hong Kong SAR, China.
authors.forename: Waiman Connie
authors.initials: WC
authors.lastname: Wong
authors.affiliation: School of Chinese Medicine, University of Hong Kong, Hong Kong SAR, China.
authors.forename: Hansen
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, University of Hong Kong, Hong Kong SAR, China.
authors.forename: Lei
authors.identifier: 0000-0002-2705-1989
authors.initials: L
authors.lastname: Gao
authors.affiliation: Guangzhou Quality R&D Center of Traditional Chinese Medicine, School of Life Science, Sun Yat-sen University, Guangzhou, 510275, China.
authors.forename: Yichu
authors.initials: Y
authors.lastname: Nie
authors.affiliation: School of Biomedical Science, University of Hong Kong, Hong Kong SAR, China, State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Hong Kong SAR, China, and Joint Laboratory for CNS Regeneration, Jinan University and University of Hong Kong, GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China shenjg@hku.hk wtwu@hku.hk.
authors.forename: Wutian
authors.initials: W
authors.lastname: Wu
authors.affiliation: School of Chinese Medicine, University of Hong Kong, Hong Kong SAR, China, shenjg@hku.hk wtwu@hku.hk.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shen
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013116:Spinal Cord / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D057705:Transendothelial and Transepithelial Migration; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
keywords: ICAM-1; VCAM-1; caveolin-1; experimental autoimmune encephalomyelitis; lymphocyte trafficking