Self-reactive IgE exacerbates interferon responses associated with autoimmunity Academic Article uri icon

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abstract

  • 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.

authors

  • Henault, Jill
  • Riggs, Jeffrey M
  • Karnell, Jodi L
  • Liarski, Vladimir M
  • Li, Jianqing
  • Shirinian, Lena
  • Xu, Linda
  • Casey, Kerry A
  • Smith, Michael A
  • Khatry, Deepak B
  • Izhak, Liat
  • Clarke, Lorraine
  • Herbst, Ronald
  • Ettinger, Rachel
  • Petri, Michelle
  • Clark, Marcus R
  • Mustelin, Tomas
  • Kolbeck, Roland
  • Sanjuan, Miguel A

publication date

  • February 2016

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