| First Author | Pfeifle R | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 1 | Pages | 104-113 |
| PubMed ID | 27820809 | Mgi Jnum | J:259152 |
| Mgi Id | MGI:6142317 | Doi | 10.1038/ni.3579 |
| Citation | Pfeifle R, et al. (2017) Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease. Nat Immunol 18(1):104-113 |
| abstractText | The checkpoints and mechanisms that contribute to autoantibody-driven disease are as yet incompletely understood. Here we identified the axis of interleukin 23 (IL-23) and the TH17 subset of helper T cells as a decisive factor that controlled the intrinsic inflammatory activity of autoantibodies and triggered the clinical onset of autoimmune arthritis. By instructing B cells in an IL-22- and IL-21-dependent manner, TH17 cells regulated the expression of beta-galactoside alpha2,6-sialyltransferase 1 in newly differentiating antibody-producing cells and determined the glycosylation profile and activity of immunoglobulin G (IgG) produced by the plasma cells that subsequently emerged. Asymptomatic humans with rheumatoid arthritis (RA)-specific autoantibodies showed identical changes in the activity and glycosylation of autoreactive IgG antibodies before shifting to the inflammatory phase of RA; thus, our results identify an IL-23-TH17 cell-dependent pathway that controls autoantibody activity and unmasks a preexisting breach in immunotolerance. |
