Resistance to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis by death receptor 6-deficient mice

Clint S. Schmidt, Jingyong Zhao, Jana Chain, Deena Hepburn, Bruce Gitter, George Sandusky, Subba Chintalacharuvu, Andrew Glasebrook, Songqing Na

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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-γ-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-γ, 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.

Original languageEnglish (US)
Pages (from-to)2286-2292
Number of pages7
JournalJournal of Immunology
Volume175
Issue number4
StatePublished - Aug 15 2005
Externally publishedYes

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Myelin-Oligodendrocyte Glycoprotein
Death Domain Receptors
Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Interleukin-4
Cytokines
Integrin alpha4beta1
Central Nervous System Diseases
Autoantigens
Demyelinating Diseases
T-Cell Antigen Receptor
Autoimmune Diseases
Spinal Cord
Leukocytes
Cell Death
Macrophages

ASJC Scopus subject areas

  • Immunology

Cite this

Resistance to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis by death receptor 6-deficient mice. / Schmidt, Clint S.; Zhao, Jingyong; Chain, Jana; Hepburn, Deena; Gitter, Bruce; Sandusky, George; Chintalacharuvu, Subba; Glasebrook, Andrew; Na, Songqing.

In: Journal of Immunology, Vol. 175, No. 4, 15.08.2005, p. 2286-2292.

Research output: Contribution to journalArticle

Schmidt, CS, Zhao, J, Chain, J, Hepburn, D, Gitter, B, Sandusky, G, Chintalacharuvu, S, Glasebrook, A & Na, S 2005, 'Resistance to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis by death receptor 6-deficient mice', Journal of Immunology, vol. 175, no. 4, pp. 2286-2292.
Schmidt, Clint S. ; Zhao, Jingyong ; Chain, Jana ; Hepburn, Deena ; Gitter, Bruce ; Sandusky, George ; Chintalacharuvu, Subba ; Glasebrook, Andrew ; Na, Songqing. / Resistance to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis by death receptor 6-deficient mice. In: Journal of Immunology. 2005 ; Vol. 175, No. 4. pp. 2286-2292.
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