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

Research output: Contribution to journalArticle

28 Citations (Scopus)

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
StatePublished - Dec 20 2011

Fingerprint

Natural Killer T-Cells
Interleukin-18
Antibody Formation
B-Lymphocytes
Cytokines
Perforin
Germinal Center
Plasma Cells
Autoimmunity
Interleukin-1
Immunoglobulin E
Immunoglobulin M
Hypersensitivity
Spleen
Immunoglobulin G
Inflammation

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

The inflammatory cytokine IL-18 induces self-reactive innate antibody responses regulated by natural killer T cells. / Enoksson, Sara Lind; Grasset, Emilie K.; Hägglöf, Thomas; Mattsson, Nina; Kaiser, Ylva; Gabrielsson, Susanne; McGaha, Tracy L.; Scheynius, Annika; Karlsson, Mikael C I.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 51, 20.12.2011.

Research output: Contribution to journalArticle

Enoksson, Sara Lind ; Grasset, Emilie K. ; Hägglöf, Thomas ; Mattsson, Nina ; Kaiser, Ylva ; Gabrielsson, Susanne ; McGaha, Tracy L. ; Scheynius, Annika ; Karlsson, Mikael C I. / The inflammatory cytokine IL-18 induces self-reactive innate antibody responses regulated by natural killer T cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 51.
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AU - Kaiser, Ylva

AU - Gabrielsson, Susanne

AU - McGaha, Tracy L.

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