期刊
NATURE IMMUNOLOGY
卷 18, 期 1, 页码 104-113出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3579
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资金
- Deutsche Forschungsgemeinschaft [CRC1181, SPP1468-IMMUNOBONE, CRC643]
- European Union [ERC StG 640087 - SOS]
- European Union (MASTERSWITCH project)
- European Union (BTCure)
- Interdisciplinary Centre for Clinical Research, Erlangen [IZKF A55, A68]
- Bundesministerium fur Bildung und Forschung (METARTHROS)
- Else-Kroner Fresenius Stiftung [2013_A274]
- ELAN Fonds of the Universiatatsklinikum Erlangen [14-10-17-1]
- Strategic Science Foundation
- KAWallenberg Fondation
- Bavarian Genome Network (BayGene)
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(H)17 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(H)17 cells regulated the expression of beta-galactoside alpha 2,6-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-T(H)17 cell-dependent pathway that controls autoantibody activity and unmasks a preexisting breach in immunotolerance.
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