| First Author | McCandless EE | Year | 2009 |
| Journal | J Immunol | Volume | 183 |
| Issue | 1 | Pages | 613-20 |
| PubMed ID | 19535637 | Mgi Jnum | J:150113 |
| Mgi Id | MGI:3849758 | Doi | 10.4049/jimmunol.0802258 |
| Citation | McCandless EE, et al. (2009) 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 183(1):613-20 |
| abstractText | 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. |
