Caveolin-1 is critical for Lymphocyte Trafficking into Central Nervous system during Experimental Autoimmune Encephalomyelitis

• DOI: 10.4049/jimmunol.196.supp.119.18
• Publication Date: 2023-01-01T10:24:20Z
• Authors: Hao Wu; Rui-xia Deng; Xing-miao Chen; Wu-tian Wu; Jian-gang Shen
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Abstract Multiple Sclerosis (MS) is a progressive autoimmune disease in central nervous system (CNS) with its pathogenesis not fully understood. In the present study, we demonstrated that caveolin-1, a major membrane scaffolding protein, plays a critical role in experimental autoimmune encephalomyelitis (EAE), a laboratory murine model of multiple sclerosis (MS). Immunized WT mice have increases of caveolin-1 expressions in serum and CNS tissues associated with disease development. After immunization, Cav-1knockout mice showed remarkable resistance with alleviated incidences and symptoms. With caveolin-1 deficiency, encephalitogenic T lymphocytes processed less efficient trafficking into CNS parenchyma, probably a sequence of declined expressions of adhesion molecule ICAM-1 and VCAM-1 in the white matter of CNS tissues. In agreement with in vivo studies, in vitro silencing of caveolin-1 in endothelial cells prevented the up-regulation of ICAM-1 expression, leading to less trans-endothelial migration of encephalitogenic TH1 and TH17 cells. Taken together, the results indicate caveolin-1 as an active modulator of lymphocyte trafficking into CNS and may be a potential therapeutic target for neuroinflammatory diseases.