C1q inhibits immune complex–induced interferon-α production in plasmacytoid dendritic cells: A novel link between C1q deficiency and systemic lupus erythematosus pathogenesis
Christian Lood
Lund University Hospital and Lund University, Lund, Sweden
Search for more papers by this authorLennart Truedsson
Lund University, Lund, Sweden
Dr. Truedsson has received consulting fees and/or honoraria from Shire Human Genetic Therapies (less than $10,000).
Search for more papers by this authorGunnar V. Alm
Swedish University of Agricultural Sciences, Uppsala, Sweden
Drs. Alm and Rönnblom have received consulting fees, speaking fees, and/or honoraria from Miltenyi Biotec (less than $10,000 each).
Search for more papers by this authorLars Rönnblom
Uppsala University, Uppsala, Sweden
Drs. Alm and Rönnblom have received consulting fees, speaking fees, and/or honoraria from Miltenyi Biotec (less than $10,000 each).
Search for more papers by this authorCorresponding Author
Anders A. Bengtsson
Lund University Hospital, Lund, Sweden
Dr. Bengtsson has received consulting fees, speaking fees, and/or honoraria from Active Biotech Research AB (less than $10,000).
Department of Clinical Sciences, Section of Rheumatology, Lund University Hospital, 223 62 Lund, SwedenSearch for more papers by this authorChristian Lood
Lund University Hospital and Lund University, Lund, Sweden
Search for more papers by this authorLennart Truedsson
Lund University, Lund, Sweden
Dr. Truedsson has received consulting fees and/or honoraria from Shire Human Genetic Therapies (less than $10,000).
Search for more papers by this authorGunnar V. Alm
Swedish University of Agricultural Sciences, Uppsala, Sweden
Drs. Alm and Rönnblom have received consulting fees, speaking fees, and/or honoraria from Miltenyi Biotec (less than $10,000 each).
Search for more papers by this authorLars Rönnblom
Uppsala University, Uppsala, Sweden
Drs. Alm and Rönnblom have received consulting fees, speaking fees, and/or honoraria from Miltenyi Biotec (less than $10,000 each).
Search for more papers by this authorCorresponding Author
Anders A. Bengtsson
Lund University Hospital, Lund, Sweden
Dr. Bengtsson has received consulting fees, speaking fees, and/or honoraria from Active Biotech Research AB (less than $10,000).
Department of Clinical Sciences, Section of Rheumatology, Lund University Hospital, 223 62 Lund, SwedenSearch for more papers by this authorAbstract
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-α (IFNα).
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. IFNα production was determined by an immunoassay.
Results
C1q significantly inhibited PBMC IFNα production induced by RNA-containing immune complexes (ICs), herpes simplex virus (HSV), and CpG DNA. C1q also inhibited PDC IFNα production induced by ICs and CpG DNA but increased PDC IFNα production induced by HSV. The regulatory role of C1q was not specific for IFNα but was also seen for interleukin-6 (IL-6), IL-8, and tumor necrosis factor α. 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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