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Regulation of autoantibody activity by the IL-23-T(H)17 axis determines the onset of autoimmune disease

Pfeifle, Rene, Rothe, Tobias, Ipseiz, Natacha ORCID:, 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

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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
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 1529-2908
Date of Acceptance: 8 September 2016
Last Modified: 26 Oct 2022 08:28

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