Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system

Shirley Shi Du Yan, Zhi Ying Wu, Hui Ping Zhang, Glaucia Furtado, Xi Chen, Shi Fang Yan, Ann Marie Schimidt, Chris Brown, Alan Stern, Juan LaFaille, Leonard Chess, David Stern, Hong Jiang

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Multiple 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-α and TCR-Β 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.

Original languageEnglish (US)
Pages (from-to)287-293
Number of pages7
JournalNature Medicine
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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T-cells
Autoimmune Experimental Encephalomyelitis
Neurology
Infiltration
Central Nervous System
T-Lymphocytes
T-Cell Antigen Receptor
Myelin Basic Protein
Transgenic Mice
Multiple Sclerosis
Leukocyte L1 Antigen Complex
Ligands
Central Nervous System Diseases
Phagocytes
Myelin Sheath
Endothelium
Rodentia
Advanced Glycosylation End Product-Specific Receptor
Peptides

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system. / Yan, Shirley Shi Du; Wu, Zhi Ying; Zhang, Hui Ping; Furtado, Glaucia; Chen, Xi; Yan, Shi Fang; Schimidt, Ann Marie; Brown, Chris; Stern, Alan; LaFaille, Juan; Chess, Leonard; Stern, David; Jiang, Hong.

In: Nature Medicine, Vol. 9, No. 3, 01.03.2003, p. 287-293.

Research output: Contribution to journalArticle

Yan, SSD, Wu, ZY, Zhang, HP, Furtado, G, Chen, X, Yan, SF, Schimidt, AM, Brown, C, Stern, A, LaFaille, J, Chess, L, Stern, D & Jiang, H 2003, 'Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system', Nature Medicine, vol. 9, no. 3, pp. 287-293. https://doi.org/10.1038/nm831
Yan, Shirley Shi Du ; Wu, Zhi Ying ; Zhang, Hui Ping ; Furtado, Glaucia ; Chen, Xi ; Yan, Shi Fang ; Schimidt, Ann Marie ; Brown, Chris ; Stern, Alan ; LaFaille, Juan ; Chess, Leonard ; Stern, David ; Jiang, Hong. / Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system. In: Nature Medicine. 2003 ; Vol. 9, No. 3. pp. 287-293.
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