C1q Deficiency Leads to the Defective Suppression of IFN-α in Response to Nucleoprotein Containing Immune Complexes
Open Access
- 15 October 2010
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 185 (8), 4738-4749
- https://doi.org/10.4049/jimmunol.1001731
Abstract
Almost all humans with homozygous deficiency of C1q develop systemic lupus erythematosus (SLE). The precise cellular mechanism(s) by which C1q prevents the development of SLE remains unclear. In this study, we tested the role of C1q in the regulation of IFN-α induced by immune complexes (ICs) in vitro, as well as the consequences of lack of C1q in vivo. Our experiments revealed that C1q preferentially promotes the binding of SLE ICs to monocytes rather than plasmacytoid dendritic cells, but this inhibition was not due to the induction of inhibitory soluble factors. The presence of C1q also altered the trafficking of ICs within monocytes such that ICs persisted in early endosomes. In patients with C1q deficiency, serum and cerebrospinal fluid levels of IFN-α and IFN-γ–inducible protein-10 levels were elevated and strongly correlated with Ro autoantibodies, demonstrating the clinical significance of these observations. These studies therefore associate C1q deficiency with defective regulation of IFN-α and provide a better understanding of the cellular mechanisms by which C1q prevents the development of IC-stimulated autoimmunity.Keywords
This publication has 76 references indexed in Scilit:
- Organization of the autoantibody repertoire in healthy newborns and adults revealed by system level informatics of antigen microarray dataProceedings of the National Academy of Sciences of the United States of America, 2009
- Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interactionThe Journal of Experimental Medicine, 2009
- Enhanced expression of interferon-inducible protein-10 correlates with disease activity and clinical manifestations in systemic lupus erythematosusClinical and Experimental Immunology, 2009
- Nature and functions of autoantibodiesNature Clinical Practice Rheumatology, 2008
- IRF9 and STAT1 are required for IgG autoantibody production and B cell expression of TLR7 in miceJCI Insight, 2008
- BDCA2/FcεRIγ Complex Signals through a Novel BCR-Like Pathway in Human Plasmacytoid Dendritic CellsPLoS Biology, 2007
- Reduced expression of C1q-mRNA in monocytes from patients with systemic lupus erythematosusClinical and Experimental Immunology, 2006
- Prostaglandin E2 is a negative regulator on human plasmacytoid dendritic cellsImmunology, 2006
- Induction of interferon‐α by immune complexes or liposomes containing systemic lupus erythematosus autoantigen– and Sjögren's syndrome autoantigen–associated RNAArthritis & Rheumatism, 2006
- Methods for the separation, purification and measurement of nine components of hemolytic complement in guinea-pig serumImmunochemistry, 1966