| Literature DB >> 27820809 |
René Pfeifle1,2, Tobias Rothe1,2, Natacha Ipseiz1,2, Hans U Scherer3, Stephan Culemann1,2, Ulrike Harre1, Jochen A Ackermann1,2, Martina Seefried2,4, Arnd Kleyer1, Stefan Uderhardt1,2, Benjamin Haugg1,2, Axel J Hueber1, Patrick Daum2,5, Gordon F Heidkamp6, Changrong Ge7, Sybille Böhm4, Anja Lux4, Wolfgang Schuh2,5, Iryna Magorivska1, Kutty S Nandakumar7, Erik Lönnblom7, Christoph Becker8, Diana Dudziak6, Manfred Wuhrer9, Yoann Rombouts3,9,10, Carolien A Koeleman9, René Toes3, Thomas H Winkler2,4, Rikard Holmdahl7, Martin Herrmann1, Stephan Blüml11, Falk Nimmerjahn4, Georg Schett1, Gerhard Krönke1,2.
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.Entities:
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Year: 2016 PMID： 27820809 PMCID： PMC5164937 DOI： 10.1038/ni.3579
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606