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IL-1R signaling within the central nervous system regulates CXCL12 expression at the blood-brain barrier and disease severity during experimental autoimmune encephalomyelitis. J Immunol 2009 Jul 01;183(1):613-20 PMID: 19535637 PMCID: PMC2892701

Pubmed ID

19535637

DOI

10.4049/jimmunol.0802258

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the CNS characterized by disruption of the blood-brain barrier (BBB). This breach in CNS immune privilege allows undeterred trafficking of myelin-specific lymphocytes into the CNS where they induce demyelination. Although the mechanism of BBB compromise is not known, the chemokine CXCL12 has been implicated as a molecular component of the BBB whose pattern of expression is specifically altered during MS and which correlates with disease severity. The inflammatory cytokine IL-1beta has recently been shown to contribute not only to BBB permeability but also to the development of IL-17-driven autoimmune responses. Using experimental autoimmune encephalomyelitis, the rodent model of MS, we demonstrate that IL-1beta mediates pathologic relocation of CXCL12 during the induction phase of the disease, before the development of BBB disruption. We also show that CD4, CD8, and, surprisingly gammadelta T cells are all sources of IL-1beta. In addition, gammadelta T cells are also targets of this cytokine, contributing to IL-1beta-mediated production of IL-17. Finally, we show that the level of CNS IL-1R determines the clinical severity of experimental autoimmune encephalomyelitis. These data suggest that T cell-derived IL-1beta contributes to loss of immune privilege during CNS autoimmunity via pathologic alteration in the expression of CXCL12 at the BBB.

Author List

McCandless EE, Budde M, Lees JR, Dorsey D, Lyng E, Klein RS

Author

Matthew Budde PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin




Scopus

2-s2.0-68949119874   55 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Blood-Brain Barrier
Chemokine CXCL12
Encephalomyelitis, Autoimmune, Experimental
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Transport
Receptors, Interleukin-1
Severity of Illness Index
Signal Transduction
Spinal Cord
jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad