Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis

Christopher Lock, Guy Hermans, Rosetta Pedotti, Andrea Brendolan, Eric Schadt, Hideki Garren, Annette Langer-Gould, Samuel Strober, Barbara Cannella, John Allard, Paul Klonowski, Angela Austin, Nagin Lad, Naftali Kaminski, Stephen J. Galli, Naftali Kaminski, Cedric S. Raine, Renu Heller, Lawrence Steinman

Research output: Contribution to journalArticle

1277 Scopus citations

Abstract

Microarray analysis of multiple sclerosis (MS) lesions obtained at autopsy revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin-6 and - 17, interferon-γ and associated downstream pathways. Comparison of two poles of MS pathologyacute lesions with inflammation versus 'silent' lesions without inflammation-revealed differentially transcribed genes. Some products of these genes were chosen as targets for therapy of experimental autoimmune encephalomyelitis (EAE) in mice. Granulocyte colony-stimulating factor is upregulated in acute, but not in chronic, MS lesions, and the effect on ameliorating EAE is more pronounced in the acute phase, in contrast to knocking out the immunoglobulin Fc receptor common γ chain where the effect is greatest on chronic disease. These results in EAE corroborate the microarray studies on MS lesions. Large-scale analysis of transcripts in MS lesions elucidates new aspects of pathology and opens possibilities for therapy.

Original languageEnglish (US)
Pages (from-to)500-508
Number of pages9
JournalNature Medicine
Volume8
Issue number5
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lock, C., Hermans, G., Pedotti, R., Brendolan, A., Schadt, E., Garren, H., Langer-Gould, A., Strober, S., Cannella, B., Allard, J., Klonowski, P., Austin, A., Lad, N., Kaminski, N., Galli, S. J., Kaminski, N., Raine, C. S., Heller, R., & Steinman, L. (2002). Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nature Medicine, 8(5), 500-508. https://doi.org/10.1038/nm0502-500