C1q Inhibits Immune Complex-Induced Interferon-alpha Production in Plasmacytoid Dendritic Cells A Novel Link Between C1q Deficiency and Systemic Lupus Erythematosus Pathogenesis

Research output: Contribution to journalArticle

Abstract

Objective. C1q deficiency is the strongest risk factor known for the development of systemic lupus erythematosus (SLE), since almost all humans with a genetic deficiency of C1q develop this disease. Low C1q serum concentration is also a typical finding in SLE during flares, emphasizing the involvement of C1q in SLE pathogenesis. Recent studies have revealed that C1q has a regulatory effect on Toll-like receptor-induced cytokine production. Therefore, we undertook this study to investigate whether C1q could regulate production of interferon-alpha (IFN alpha). Methods. Peripheral blood mononuclear cells (PBMCs) and plasmacytoid dendritic cells (PDCs) were stimulated with 3 known interferogenic stimuli and cultured with physiologic concentrations of C1q. IFN alpha production was determined by an immunoassay. Results. C1q significantly inhibited PBMC IFN alpha production induced by RNA-containing immune complexes (ICs), herpes simplex virus (HSV), and CpG DNA. C1q also inhibited PDC IFN alpha production induced by ICs and CpG DNA but increased PDC IFNa production induced by HSV. The regulatory role of C1q was not specific for IFN alpha but was also seen for interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha. We demonstrated binding of C1q to PDCs both by surface plasmon resonance interaction analysis and by flow cytometry, and we also demonstrated intracellular detection of 2 C1q binding proteins. Conclusion. Our findings contribute to the understanding of why C1q deficiency is such a strong risk factor for SLE and suggest an explanation for the up-regulation of the type I IFN system seen in SLE patients.

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  • Rheumatology and Autoimmunity
Original languageEnglish
Pages (from-to)3081-3090
JournalArthritis and Rheumatism
Volume60
Issue number10
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes

Related research output

Lood, C., 2012, Section of Rheumatology, Dept of Clinical Sciences, Lund. 84 p.

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