Insoluble immune complexes are most effective at triggering IL-10 production in human monocytes and synergize with TLR ligands and C5a

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Stephen J DiMartinoJ E Salmon

Abstract

In systemic lupus erythematosus (SLE), a disease of immune complex (IC) deposition, interleukin-10 (IL-10) is thought to promote B-lymphocyte hyperactivity and autoantibody production. Both ICs and Toll-like receptor (TLR) ligands have been shown to stimulate the production of IL-10 by human monocytes. Using an in vitro model, we studied how IC solubility, complement activation products, and TLR ligands could affect IL-10 production by human monocytes stimulated with ICs. Human monocytes were stimulated with soluble or insoluble heat-aggregated human IgG with or without TLR ligands or C5a. Cytokine levels in cell culture supernatants were measured by ELISA. To study cytokine signaling, cell lysates were analyzed by Western blot for total or tyrosine-phosphorylated STAT3. Insoluble ICs were most effective at stimulating production of IL-10, and costimulation LPS enhanced synthesis of IL-10. In addition, stimulation with insoluble ICs together with C5a enhanced the production of IL-10 by 2-4 fold in either the presence or absence of TLR ligands. Increased STAT3 phosphorylation correlated temporally with enhanced IL-10 production and was reduced by an IL-10 receptor blocking antibody, suggesting that IL-10 was responsible for obse...Continue Reading

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Citations

May 28, 2013·Clinical Rheumatology·Hui PengDong-Qing Ye
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May 26, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joong-Hyuk SheenPeter S Heeger

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