Regulation of autoantibody activity by the IL-23-T_H17 axis determines the onset of autoimmune disease.

ABSTRACT: 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 T_H17 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, T_H17 cells regulated the expression of β-galactoside α2,6-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 cha

SUBMITTER: Pfeifle R 

PROVIDER: S-EPMC5164937 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature