TNFR1-dependent VCAM-1 expression by astrocytes exposes the CNS to destructive inflammation.
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.
Gimenez
Mary Ann T
MA
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Sim
Julia E
JE
Russell
John H
JH
D019264:Adoptive Transfer; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D018124:Receptors, Tumor Necrosis Factor; D019010:Vascular Cell Adhesion Molecule-1