Regulation of autoantibody activity by the IL-23–TH17 axis determines the onset of autoimmune disease
| Autor: | Stephan Blüml, Tobias Rothe, Wolfgang Schuh, René E. M. Toes, Yoann Rombouts, Gerhard Krönke, Martin Herrmann, Patrick Daum, Iryna Magorivska, Erik Lönnblom, Axel J. Hueber, R Pfeifle, Kutty Selva Nandakumar, Martina Seefried, Gordon F. Heidkamp, Changrong Ge, Carolien A. M. Koeleman, Christoph Becker, Sybille Böhm, Stephan Culemann, Stefan Uderhardt, Rikard Holmdahl, Arnd Kleyer, Thomas Winkler, Benjamin Haugg, Georg Schett, Falk Nimmerjahn, Ulrike Harre, Anja Lux, Diana Dudziak, Hans Scherer, Jochen A. Ackermann, Manfred Wuhrer, Natacha Ipseiz |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Glycosylation Immunology Autoimmunity medicine.disease_cause Lymphocyte Activation Interleukin-23 Immunoglobulin G Article Arthritis Rheumatoid 03 medical and health sciences chemistry.chemical_compound Mice medicine Interleukin 23 Immune Tolerance Immunology and Allergy Animals Humans beta-D-Galactoside alpha 2-6-Sialyltransferase Cells Cultured Autoantibodies Autoimmune disease B-Lymphocytes biology business.industry Interleukins Autoantibody Cell Differentiation medicine.disease Sialyltransferases 3. Good health Mice Inbred C57BL Disease Models Animal 030104 developmental biology chemistry Rheumatoid arthritis biology.protein Th17 Cells Antibody business Signal Transduction |
| Zdroj: | Nature Immunology Nature Immunology, 18(1), 104-113 |
| ISSN: | 1529-2908 |
| DOI: | 10.1038/ni.3579 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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