Regulation of autoantibody activity by the IL-23–TH17 axis determines the onset of autoimmune disease
- 7 November 2016
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 18 (1), 104-113
- https://doi.org/10.1038/ni.3579
Abstract
Krönke and colleagues show that the cytokine IL-23 controls the glycosylation profile and inflammatory activity of autoantibodies through control of sialyltransferase activity in plasma cells mediated by the TH17 subset of helper T cells. 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 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 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.Keywords
This publication has 42 references indexed in Scilit:
- Autoantibody Profiling in Multiple Sclerosis Using Arrays of Human Protein FragmentsMolecular & Cellular Proteomics, 2013
- T cell–independent B cell activation induces immunosuppressive sialylated IgG antibodiesJCI Insight, 2013
- IL-23 Dependent and Independent Stages of Experimental Arthritis: No Clinical Effect of Therapeutic IL-23p19 Inhibition in Collagen-induced ArthritisPLOS ONE, 2013
- Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled studyAnnals Of The Rheumatic Diseases, 2012
- The Pathogenesis of Rheumatoid ArthritisThe New England Journal of Medicine, 2011
- Proinflammatory T helper type 17 cells are effective B-cell helpersProceedings of the National Academy of Sciences of the United States of America, 2010
- Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via T Helper 17 CellsImmunity, 2010
- Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: a cohort studyArthritis Research & Therapy, 2010
- Recapitulation of IVIG Anti-Inflammatory Activity with a Recombinant IgG FcScience, 2008
- Induction and Suppression of Collagen-Induced Arthritis Is Dependent on Distinct Fcγ ReceptorsThe Journal of Experimental Medicine, 2000