Self-reactive IgE exacerbates interferon responses associated with autoimmunity

• DOI: 10.1038/ni.3326
• Publication Date: 2015-12-21T17:13:10Z
• Authors: Jill Henault; Jeffrey M Riggs; Jodi L Karnell; Vladimir M Liarski; Jianqing Li; Lena Shirinian; Linda Xu; Kerry A Casey; Michael A Smith; Deepak B Khatry; Liat Izhak; Lorraine Clarke; Ronald Herbst; Rachel Ettinger; Michelle Petri; Marcus R Clark; Tomas Mustelin; Roland Kolbeck; Miguel A Sanjuan
• Keywords: Male; B-Lymphocytes; Plasma Cells; Autoimmunity; Antigen-Antibody Complex; Dendritic Cells; Immunoglobulin E; Lupus Nephritis; Article; 3. Good health; Phagocytosis; Antibodies, Antinuclear; Immunoglobulin G; Phagosomes; Toll-Like Receptor 9; Leukocytes, Mononuclear; Cytokines; Humans; Lupus Erythematosus, Systemic; Female; Interferons; Autoantibodies

Canonically, immunoglobulin E (IgE) mediates allergic immune responses by triggering mast cells and basophils to release histamine and type 2 helper cytokines. Here we found that in human systemic lupus erythematosus (SLE), IgE antibodies specific for double-stranded DNA (dsDNA) activated plasmacytoid dendritic cells (pDCs), a type of cell of the immune system linked to viral defense, which led to the secretion of substantial amounts of interferon-α (IFN-α). The concentration of dsDNA-specific IgE found in patient serum correlated with disease severity and greatly potentiated pDC function by triggering phagocytosis via the high-affinity FcɛRI receptor for IgE, followed by Toll-like receptor 9 (TLR9)-mediated sensing of DNA in phagosomes. Our findings expand the known pathogenic mechanisms of IgE-mediated inflammation beyond those found in allergy and demonstrate that IgE can trigger interferon responses capable of exacerbating self-destructive autoimmune responses.