Nature Medicine
9, 287 - 293 (2003)
Published online: 24 February 2003; | doi:10.1038/nm831
Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous systemShirley ShiDu Yan1, Zhi-Ying Wu1, 2, Hui Ping Zhang1, Glaucia Furtado3, Xi Chen4, Shi Fang Yan1, Ann Marie Schmidt1, Chris Brown1, Alan Stern1, Juan Lafaille3, Leonard Chess1, David M. Stern1, 5
& Hong Jiang11
Departments of Pathology, Surgery, Medicine, and Physiology and Cellular Biophysics, College of Physicians and Surgeons of Columbia University, New York, New York, USA
2
Department of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, People's Republic of China
3
Skirball Institute of Biomedical Science, New York University, New York, New York, USA
4
Department of Neurology, New York University Medical Center, New York, New York, USA
5
School of Medicine, Medical College of Georgia, Augusta, Georgia, USA
Correspondence should be addressed to Shirley ShiDu Yan sdy1@columbia.eduMultiple sclerosis (MS) is a devastating neuroinflammatory disorder of the central nervous system (CNS) in which T cells that are reactive with major components of myelin sheaths have a central role. The receptor for advanced glycation end products (RAGE) is present on T cells, mononuclear phagocytes and endothelium. Its pro-inflammatory ligands, S100-calgranulins, are upregulated in MS and in the related rodent model, experimental autoimmune encephalomyelitis (EAE). Blockade of RAGE suppressed EAE when disease was induced by myelin basic protein (MBP) peptide or encephalitogenic T cells, or when EAE occurred spontaneously in T-cell receptor (TCR)-transgenic mice devoid of endogenous TCR- and TCR- chains. Inhibition of RAGE markedly decreased infiltration of the CNS by immune and inflammatory cells. Transgenic mice with targeted overexpression of dominant-negative RAGE in CD4+ T cells were resistant to MBP-induced EAE. These data reinforce the importance of RAGE-ligand interactions in modulating properties of CD4+ T cells that infiltrate the CNS.
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