Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease.

Journal article


Publication Details

Author(s): Pfeifle R, Rothe T, Ipseiz N, Scherer HU, Culemann S, Harre U, Ackermann JA, Seefried M, Kleyer A, Uderhardt S, Haugg B, Huebert AJ, Daum P, Heidkamp GF, Ge C, Böhm S, Lux A, Schuh W, Magorivskal I, Nandakumar KS, Loennblom E, Becker C, Dudziak D, Wuhrer M, Rombouts Y, Koeleman CA, Toes R, Winkler TH, Holmdahl R, Herrmann M, Blueml S, Nimmerjahn F, Schett G, Krönke G, Winkler T
Journal: Nature immunology
Publication year: 2017
Volume: 18
Journal issue: 1
Pages range: 104-113
ISSN: 1529-2916


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.



FAU Authors / FAU Editors

Böhm, Sybille
Lehrstuhl für Genetik
Daum, Patrick
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie
Dudziak, Diana Prof. Dr.
Professur für die Biologie Dendritischer Zellen
Heidkamp, Gordon Frederik
Hautklinik
Herrmann, Martin Prof. Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Ipseiz, Natacha
Lehrstuhl für Genetik
Kleyer, Arnd Dr. med.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Krönke, Gerhard Prof. Dr. med.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Lux, Anja Dr.
Lehrstuhl für Genetik
Nimmerjahn, Falk Prof. Dr.
Lehrstuhl für Genetik
Pfeifle, René Dr. rer. nat.
Lehrstuhl für Genetik
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III
Seefried, Martina
Sonderforschungsbereich 643 Strategien der zellulären Immunintervention (Sprecher: Prof.Dr.Schuler)
Winkler, Thomas Prof. Dr.
Professur für Genetik


External institutions with authors

Karolinska Institute
Leiden University
Medizinische Universität Wien


How to cite

APA:
Pfeifle, R., Rothe, T., Ipseiz, N., Scherer, H.U., Culemann, S., Harre, U.,... Winkler, T. (2017). Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease. Nature immunology, 18(1), 104-113. https://dx.doi.org/10.1038/ni.3579

MLA:
Pfeifle, René, et al. "Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease." Nature immunology 18.1 (2017): 104-113.

BibTeX: 

Last updated on 2019-18-07 at 07:17