Death receptor 6 contributes to autoimmunity in lupus-prone mice

Daisuke Fujikura (), Masahiro Ikesue, Tsutomu Endo, Satoko Chiba, Hideaki Higashi and Toshimitsu Uede ()
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Daisuke Fujikura: 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
Hideaki Higashi: Hokkaido University Research Center for Zoonosis Control
Toshimitsu Uede: Hokkaido University Institute for Genetic Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms13957

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