Self-reactive IgE exacerbates interferon responses associated with autoimmunity

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

Research output: Contribution to journalArticlepeer-review

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 Fc RI 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.

Original languageEnglish (US)
Pages (from-to)196-203
Number of pages8
JournalNature Immunology
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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