The inflammatory cytokine IL-18 induces self-reactive innate antibody responses regulated by natural killer T cells

Sara Lind Enoksson, Emilie K. Grasset, Thomas Hägglöf, Nina Mattsson, Ylva Kaiser, Susanne Gabrielsson, Tracy L. McGaha, Annika Scheynius, Mikael C I Karlsson

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33 Scopus citations

Abstract

Inflammatory responses initiate rapid production of IL-1 family cytokines, including IL-18. This cytokine is produced at high levels in inflammatory diseases, including allergy and autoimmunity, and is known to induce IgE production in mice. Here we provide evidence that IL-18 is directly coupled to induction of self-reactive IgM and IgG antibody responses and recruitment of innate B2 B cells residing in the marginal zone of the spleen. Moreover, the data suggest that the B-cell activation occurs predominantly in splenic extrafollicular plasma cell foci and is regulated by natural killer T (NKT) cells that prevent formation of mature germinal centers. We also find evidence that NKT cells control this type of B-cell activation via cytotoxicity mediated by both the perforin and CD95/CD178 pathways. Thus, NKT cells regulate innate antibody responses initiated by an inflammatory stimulus, suggesting a general mechanism that regulates B-cell behavior in inflammation and autoreactivity.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number51
DOIs
Publication statusPublished - Dec 20 2011

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Keywords

  • Anti-DNA antibodies
  • Biological sciences
  • Immunology
  • Marginal zone B cells

ASJC Scopus subject areas

  • General

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