Apoptotic cell-mediated immunoregulation of dendritic cells does not require iC3b opsonization

The Journal of Immunology : Official Journal of the American Association of Immunologists
Edward M BehrensStefania Gallucci

Abstract

A number of recent studies show that activation of CR3 on dendritic cells (DCs) suppresses TLR-induced TNF-alpha and IL-12 production and inhibits effective Ag presentation. Although the proposed physiologic role for these phenomena is immune suppression due to recognition of iC3b opsonized apoptotic cells by CR3, all of the aforementioned investigations used artificial means of activating CR3. We investigated whether iC3b opsonized apoptotic cells could induce the same changes reported with artificial ligands such as mAbs or iC3b-opsonized RBC. We explored the kinetics of iC3b opsonization in two models of murine cell apoptosis, gamma-irradiated thymocytes and cytokine deprivation of the IL-3 dependent cell line BaF3. Using a relatively homogenous population of early apoptotic cells (IL-3 deprived BaF3 cells), we show that iC3b opsonized apoptotic cells engage CR3, but this interaction is dispensable in mediating the anti-inflammatory effects of apoptotic cells. TLR-induced TNF-alpha and IL-12 production by bone marrow-derived DCs occurs heterogeneously, with apoptotic cells inhibiting only certain populations depending on the TLR agonist. In contrast, although apoptotic cells induced homogeneous IL-10 production by DCs, IL-10...Continue Reading

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Citations

Feb 9, 2010·Apoptosis : an International Journal on Programmed Cell Death·Adrian E Morelli, Adriana T Larregina
Jun 12, 2013·Lupus·S C FagerholmC S Lau
May 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yifang ChenGregg J Silverman
Jan 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Lucie BaudinoMarina Botto
Oct 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Deborah A FraserAndrea J Tenner

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