The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

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

På svenska

Author

Summary, in English

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.

Publishing year

2009

Language

English

Pages

3081-3090

Publication/Series

Arthritis and Rheumatism

Volume

60

Issue

10

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Rheumatology and Autoimmunity

Status

Published

ISBN/ISSN/Other

  • ISSN: 1529-0131