| First Author | Schmidt CS | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 4 | Pages | 2286-92 |
| PubMed ID | 16081797 | Mgi Jnum | J:107509 |
| Mgi Id | MGI:3621339 | Doi | 10.4049/jimmunol.175.4.2286 |
| Citation | Schmidt CS, et al. (2005) Resistance to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis by death receptor 6-deficient mice. J Immunol 175(4):2286-92 |
| abstractText | Genetic disruption of death receptor 6 (DR6) results in enhanced CD4+ T cell expansion, Th2 differentiation, and humoral responses after stimulation. However, the in vivo consequences of DR6 targeting (DR6-/-) during the initiation and progression of inflammatory autoimmune disease are unclear. Using a myelin oligodendrocyte glycoprotein (MOG(35-55))-induced model of experimental autoimmune encephalomyelitis, DR6-/- mice were found to be highly resistant to both the onset and the progression of CNS disease compared with wild-type (WT) littermates. DR6-/- mice exhibited fewer inflammatory foci along with minimal demyelination and perivascular cuffing of inflammatory cells. Consistent with these observations, mononuclear cell infiltration, including CD4+ T cells and macrophages, in the spinal cord of DR6-/- mice was dramatically reduced. Furthermore, CD4+ T cells from DR6-/- mice exhibited profoundly reduced cell surface expression of VLA-4 before and after stimulation. Compared with WT mice, DR6-/- mice exhibited significantly increased autoantigen-induced T cell proliferative responses along with greater numbers of IL-4-producing and similar or slightly higher numbers of IFN-gamma-producing CD4+ T cells. DR6-/- CD4+ T cells secreted higher levels of the Th2 cytokine, IL-4, and similar levels of the Th1 cytokine, IFN-gamma, compared with WT cells. Taken together, our data demonstrate that DR6 plays an important role in regulating leukocyte infiltration and function in the induction and progression of experimental autoimmune encephalomyelitis. |
