Pfeifle, Rene, Rothe, Tobias, Ipseiz, Natacha ORCID: https://orcid.org/0000-0001-5008-8889, Scherer, Hans U., Culemann, Stephan, Harre, Ulrike, Ackermann, Jochen A., Seefried, Martina, Kleyer, Arnd, Uderhardt, Stefan, Haugg, Benjamin, Huebert, Axel J., Daum, Patrick, Heidkamp, Gordon F., Ge, Changrong, Boehm, Sybille, Lux, Anja, Schuh, Wolfgang, Magorivskal, Iryna, Nandakumar, Kutty S., Loennblom, Erik, Becker, Christoph, Dudziak, Diana, Wuhrer, Manfred, Rombouts, Yoann, Koeleman, Carolien A., Toes, Rene, Winkler, Thomas H., Holmdahl, Rikard, Herrmann, Martin, Blueml, Stephan, Nimmerjahn, Falk, Schett, Georg and Kroenke, Gerhard 2017. Regulation of autoantibody activity by the IL-23-T(H)17 axis determines the onset of autoimmune disease. Nature Immunology 18 (1) , pp. 104-113. 10.1038/ni.3579 |
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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Publisher: | Nature Publishing Group |
ISSN: | 1529-2908 |
Date of Acceptance: | 8 September 2016 |
Last Modified: | 10 Jun 2023 01:45 |
URI: | https://orca.cardiff.ac.uk/id/eprint/127540 |
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