Disease relevance of Tnfrsf21

• 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 [1].
• DR6-/- mice exhibited fewer inflammatory foci along with minimal demyelination and perivascular cuffing of inflammatory cells [1].
• Recipients of DR6 KO T cells exhibit earlier systemic symptoms of GVHD, more rapid weight loss, earlier histopathological organ damage in the thymus, spleen, and intestines, and earlier mortality [2].
• However, the in vivo consequences of DR6 targeting (DR6-/-) during the initiation and progression of inflammatory autoimmune disease are unclear [1].
• 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 [1].

High impact information on Tnfrsf21

• In addition, DR6(-/-) B cells exhibited higher surface levels of CD86 upon activation and were more effective as antigen-presenting cells in an allogeneic T cell proliferation response [3].
• This is the first demonstration of a regulatory role of DR6 in the activation and function of B cells [3].
• DR6(-/-) mice exhibited enhanced germinal center formation and increased titers of immunoglobulins to T-dependent as well as T-independent type I and II antigens [3].
• In vitro, DR6(-/-) B cells undergo increased proliferation in response to anti-immunoglobulin M, anti-CD40, and lipopolysaccharide [3].
• Genetic disruption of death receptor 6 (DR6) results in enhanced CD4+ T cell expansion, Th2 differentiation, and humoral responses after stimulation [1].

Biological context of Tnfrsf21

• Mutational analysis of the Nas1 promoter resulted in identification of a direct repeat 6-type vitamin-D-responsive element (DR6 VDRE) at -525 to -508 and an imperfect inverted repeat 0-type T(3)-responsive element (IR0 T(3)RE) at -436 to -425 which conferred 1,25-(OH)(2)D(3) and T(3) responsiveness, respectively [4].

Anatomical context of Tnfrsf21

• Similar to T cells, DR6 is expressed on resting B cells but is down-regulated upon activation [3].
• Consistent with these observations, mononuclear cell infiltration, including CD4+ T cells and macrophages, in the spinal cord of DR6-/- mice was dramatically reduced [1].
• The fourth type of antibodies, ER-TR7, detects the reticular fibroblasts of the thymus [5].
• Golli immunoreactivity appeared to colocalize with ER-TR7, a putative marker of connective tissue in lymphoid organs [6].
• DR6(-/-) mice were protected from the development of airway inflammation as evidenced by attenuated eosinophil accumulation and reduced mucus-producing cells in the lining airways of allergen-challenged animals [7].

Regulatory relationships of Tnfrsf21

• Resistance to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis by death receptor 6-deficient mice [1].

Other interactions of Tnfrsf21

• 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 [1].
• Accelerated onset and increased severity of acute graft-versus-host disease following adoptive transfer of DR6-deficient T cells [2].
• Furthermore, CD4+ T cells from DR6-/- mice exhibited profoundly reduced cell surface expression of VLA-4 before and after stimulation [1].

References