Activation of type I interferon in systemic lupus erythematosus

Abstract

Type I interferon (IFN) has been implicated in the pathogenesis of systemic lupus erythematosus (SLE) since the late 1970s when elevated serum levels were noted in patients with this autoimmune disease. More recently, the ability of SLE sera to induce IFN in normal peripheral blood mononuclear cells has been noted and led to the recognition of RNA/DNA-containing immune complexes as key components of this IFN-inducing factor. Interest in the field grew with the publication of several gene expression studies that documented activation of the type I IFN pathway in patients with SLE. This activation was associated with disease activity and severity. The important implications of these advances for the management of patients with SLE are twofold. First, IFN may be a useful biomarker of disease subtype and activity and, second, IFN is a rational target for therapeutic intervention. Cautious blockade of this pathway might eliminate an important contributor to autoimmunity.

Keywords::

• plasmacytoid dendritic cell
• systemic lupus erythematosus
• Toll-like receptor
• type I interferon

Acknowlegements

NIH AI052422 and AI059893; Mary Kirkland Center for Lupus Research; Alliance for Lupus Research; Stavros Niarchos Fellowship of the Arthritis Foundation, New York Chapter.

Notes

CXCL9: C-X-C motif, ligand 9; IFN: Interferon; MCP: Monocyte chemotactic protein; STAT: Signal transducers and activators of transcription; TNF: Tumor necrosis factor.

BDCA: Blood dendritic cell antigen; DC: Dendritic cell; IFN: Interferon; TLR: Toll-like receptor.