{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:25:23Z","timestamp":1788672323772,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T00:00:00Z","timestamp":1372723200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>C\u2010reactive protein (CRP) is a serum pattern recognition molecule that binds to apoptotic cells and nucleoprotein autoantigens and Fc\u03b3 receptors (Fc\u03b3R). In systemic lupus erythematosus (SLE), immune complexes (ICs) containing nucleoprotein autoantigens activate plasmacytoid dendritic cells (PDCs) to produce type I interferon (IFN), which contributes to disease pathogenesis. Autoantibody ICs are taken up by PDCs through Fc\u03b3R type IIa into endosomes, where the nucleic acid components activate Toll\u2010like receptor 7 (TLR\u20107) or TLR\u20109. The objective of this study was to investigate the effect of CRP on PDC and monocyte responses to nucleoprotein autoantigens and ICs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood mononuclear cells (PBMCs), purified monocytes, and PDCs were isolated from healthy volunteers and stimulated with autoantibody ICs containing apoptotic cells, small nuclear RNPs (snRNPs), or DNA, or directly with TLR\u20107 and TLR\u20109 agonists. Supernatants were analyzed for IFN\u03b1 and cytokine levels by enzyme\u2010linked immunosorbent assay and multiplex assay. Small nuclear RNPs were fluorescence\u2010labeled, and the effect of CRP on binding, uptake, and intracellular localization of autoantibody snRNP complexes was measured by flow cytometry and confocal microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CRP bound to autoantigen did not induce IFN\u03b1 in PBMCs or PDCs, whereas complexes formed with autoantibody did. Significantly, CRP inhibited the IFN\u03b1 response to both anti\u2013U1 RNP\u2013snRNP complexes and anti\u2010DNA\u2013DNA complexes, but not to other TLR\u20107 and TLR\u20109 agonists. CRP directly inhibited PDC IFN\u03b1 release, promoted PDC differentiation, and increased late endosome localization of autoantigen in PDCs and monocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CRP is a regulator of the type I IFN response to SLE ICs. CRP increased the intracellular processing of ICs in late endosomes, which is associated with decreased synthesis of type I IFN after intracellular TLR activation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37968","type":"journal-article","created":{"date-parts":[[2013,4,10]],"date-time":"2013-04-10T19:18:39Z","timestamp":1365621519000},"page":"1891-1901","source":"Crossref","is-referenced-by-count":29,"title":["C\u2010Reactive Protein Inhibits Plasmacytoid Dendritic Cell Interferon Responses to Autoantibody Immune Complexes"],"prefix":"10.1002","volume":"65","author":[{"given":"Carolyn","family":"Mold","sequence":"first","affiliation":[{"name":"University of New Mexico Health Sciences Center Albuquerque"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry W. Du","family":"Clos","sequence":"additional","affiliation":[{"name":"University of New Mexico Health Sciences Center and Raymond G. 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