Format

Send to

Choose Destination
Nat Immunol. 2017 Jan;18(1):104-113. doi: 10.1038/ni.3579. Epub 2016 Nov 7.

Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease.

Author information

1
Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany.
2
Nikolaus-Fiebiger Center for Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
3
Department of Rheumatology, Leiden University Medical Centre, Leiden, the Netherlands.
4
Institute of Genetics at the Department of Biology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
5
Division of Molecular Immunology, Department of Internal Medicine 3, University Hospital Erlangen, Erlangen, Germany.
6
Department of Dermatology, Laboratory of Dendritic Cell Biology, University Hospital Erlangen, Erlangen, Germany.
7
Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
8
Department of Medicine 1, University Hospital Erlangen, Erlangen, Germany.
9
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands.
10
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France.
11
Division of Rheumatology, Internal Medicine 3, Medical University Vienna, Vienna, Austria.

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 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.

PMID:
27820809
PMCID:
PMC5164937
DOI:
10.1038/ni.3579
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center