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Death receptor 6 contributes to autoimmunity in lupus-prone mice

Author

Listed:
  • Daisuke Fujikura

    (Hokkaido University Research Center for Zoonosis Control
    Hokkaido University Institute for Genetic Medicine
    Hokkaido University Research Center for Zoonosis Control)

  • Masahiro Ikesue

    (Hokkaido University Institute for Genetic Medicine)

  • Tsutomu Endo

    (Hokkaido University Institute for Genetic Medicine)

  • Satoko Chiba

    (Hokkaido University Research Center for Zoonosis Control
    Hokkaido University Research Center for Zoonosis Control)

  • Hideaki Higashi

    (Hokkaido University Research Center for Zoonosis Control)

  • Toshimitsu Uede

    (Hokkaido University Institute for Genetic Medicine)

Abstract

Expansion of autoreactive follicular helper T (Tfh) cells is tightly restricted to prevent induction of autoantibody-dependent immunological diseases, such as systemic lupus erythematosus (SLE). Here we show expression of an orphan immune regulator, death receptor 6 (DR6/TNFRSF21), on a population of Tfh cells that are highly expanded in lupus-like disease progression in mice. Genome-wide screening reveals an interaction between syndecan-1 and DR6 resulting in immunosuppressive functions. Importantly, syndecan-1 is expressed specifically on autoreactive germinal centre (GC) B cells that are critical for maintenance of Tfh cells. Syndecan-1 expression level on GC B cells is associated with Tfh cell expansion and disease progression in lupus-prone mouse strains. In addition, Tfh cell suppression by DR6-specific monoclonal antibody delays disease progression in lupus-prone mice. These findings suggest that the DR6/syndecan-1 axis regulates aberrant GC reactions and could be a therapeutic target for autoimmune diseases such as SLE.

Suggested Citation

  • Daisuke Fujikura & Masahiro Ikesue & Tsutomu Endo & Satoko Chiba & Hideaki Higashi & Toshimitsu Uede, 2017. "Death receptor 6 contributes to autoimmunity in lupus-prone mice," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms13957
    DOI: 10.1038/ncomms13957
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