TNFR1-dependent VCAM-1 expression by astrocytes exposes the CNS to destructive inflammation

Mary Ann T. Gimenez, Julia E. Sim, John H. Russell

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

VCAM-1 is an adhesion molecule that is important to leukocyte movement across the blood-brain barrier and is involved in the formation of destructive CNS inflammatory lesions in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). We examined VCAM-1 expression in the CNS of animals with passively induced EAE and found abundant expression not only on the CNS endothelium but also on astrocytes. We show that tumor necrosis factor receptor-1 (TNFR1) signaling is required for VCAM-1 expression by astrocytes, not the vascular endothelium. In addition, we demonstrate that VCAM-1 expression by astrocytes is crucial for T cell entry into the CNS parenchyma and is required for manifestation of neurological disease.

Original languageEnglish
Pages (from-to)116-125
Number of pages10
JournalJournal of Neuroimmunology
Volume151
Issue number1-2
DOIs
StatePublished - Jun 1 2004

Keywords

  • Astrocyte
  • Experimental autoimmune encephalomyelitis
  • Inflammation
  • Multiple sclerosis
  • T cell

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