Activation of the interferon‐γ signaling pathway in systemic lupus erythematosus peripheral blood mononuclear cells

Abstract

Conclusion. In addition to supporting the role of IFNs in SLE immunopathogenesis in general, the findings of the present study support a role of IFN␥ in this disease.Type I interferons (e.g., IFN␣) and type II IFN (IFN␥) have both been implicated in the immunopathogenesis of systemic lupus erythematosus (SLE). IFN␣ and IFN␥ serum levels are increased (1-5), and IFN messenger RNA (mRNA) signatures are expressed in the peripheral blood cells of SLE patients (6-8). IFN␣ and IFN␥ are known to induce SLE flares and druginduced lupus (9-11). In murine models of the disease, both IFN␣ and IFN␥ may be pathogenetically important (12-15), and, especially, a deficiency in either IFN␥ or the IFN␥ receptor (IFN␥R) totally abates the disease process (16)(17)(18)(19).IFNs act on a variety of cells, including lymphocytes and monocytes (20,21). The biologic effects of IFN␣ and IFN␥ are mediated via the phosphorylation, and thus the activation, of members of the STAT family

Scavenging nucleic acid debris to combat autoimmunity and infectious disease

“…This in turn results in further downstream activation of signaling pathways and production of proinflammatory cytokines (15,40). In fact, multiple autoimmune disorders are characterized by elevated levels of circulating proinflammatory cytokines and autoantibodies (41)(42)(43). To date, numerous studies and clinical trials have focused on addressing circulating self-RNA and DNA, TLR activation, proinflammatory cytokines and circulating autoantibodies (16).…”

FcγRIIIa-Syk Co-signal Modulates CD4+ T-cell Response and Up-regulates Toll-like Receptor (TLR) Expression

“…IFNs are critical in RA and SLE pathogenesis (25,73,74). DNA-and RNA-containing ICs trigger IFN-␣ production from plasmacytoid dendritic cells by engaging Fc␥RIIa with TLR7 and TLR9 (34,75).…”

T Cell Targeted Therapies in Lupus: Do They Make Sense?

“…Induction of Th1 responses and IFNγ production that occur in a subset of lupus patients may culminate in a more chronic, later stage organ inflammation, and fibrosing complications [61]. IFNγ, a pleotropic type II IFN that activates macrophages, NK cells, and cytotoxic T cells and can modulate the Th and Treg cellular functions, has been implicated in lupus pathogenesis in animal models and humans.…”

“…IFNγ, a pleotropic type II IFN that activates macrophages, NK cells, and cytotoxic T cells and can modulate the Th and Treg cellular functions, has been implicated in lupus pathogenesis in animal models and humans. Expression of IFNγ inducible genes was increased in monocytes from patients with SLE [61]. AMG 811, a fully human monoclonal antibody to IFNγ has evolved to a phase Ib, randomized, dose-escalation study in SLE patients with or without glomerulonephritis [NCT00818948].…”