Journal
JOURNAL OF IMMUNOLOGY
Volume 183, Issue 1, Pages 613-620Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0802258
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Funding
- National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS059560]
- National Multiple Sclerosis Society [RG3982]
- Dana Foundation
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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-1 beta 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-1 beta 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 gamma delta T cells are all sources of IL-1 beta. In addition gamma delta T cells are also targets of this cytokine, contributing to IL-1 beta-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-1 beta contributes to loss of immune privilege during CNS autoimmunity via pathologic alteration in the expression of CXCL12 at the BBB. The Journal of Immunology, 2009, 183: 613-620.
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