| First Author | Fujikura D | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 13957 | PubMed ID | 28045014 |
| Mgi Jnum | J:244078 | Mgi Id | MGI:5912857 |
| Doi | 10.1038/ncomms13957 | Citation | Fujikura D, et al. (2017) Death receptor 6 contributes to autoimmunity in lupus-prone mice. Nat Commun 8:13957 |
| abstractText | 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. |
