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

Pfeifle R, Rothe T, Ipseiz N, Scherer HU, Culemann S, Harre U, Ackermann J, 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 T, Holmdahl R, Herrmann M, Blueml S, Nimmerjahn F, Schett G, Krönke G (2017)

Publication Status: Published

Publication Type: Journal article

Publication year: 2017

Journal

Nature Immunology Nature Research

Book Volume: 18

Pages Range: 104-113

Journal Issue: 1

DOI: 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.

Authors with CRIS profile

René Pfeifle Lehrstuhl für Genetik Tobias Rothe Department of Medicine 3 – Rheumatology and Immunology Natacha Ipseiz Lehrstuhl für Genetik Stephan Culemann Lehrstuhl für Genetik Ulrike Steffen Department of Medicine 3 – Rheumatology and Immunology Martina Seefried Arnd Kleyer Department of Medicine 3 – Rheumatology and Immunology Patrick Daum Institut für Experimentelle und Klinische Pharmakologie und Toxikologie Gordon Frederik Heidkamp Department of Dermatology Sybille Böhm Lehrstuhl für Genetik Anja Lux Lehrstuhl für Genetik Wolfgang Schuh Department of Molecular Immunology Christoph Becker Professur für Molekulare Gastroenterologie Diana Dudziak Professur für die Biologie Dendritischer Zellen Thomas Winkler Professur für Genetik Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology Falk Nimmerjahn Lehrstuhl für Genetik Georg Schett Lehrstuhl für Innere Medizin III Gerhard Krönke Professur für Modulation von Immunantworten

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung (IZKF)

Involved external institutions

Karolinska Institute SE Sweden (SE) Leiden University NL Netherlands (NL) Medizinische Universität Wien AT Austria (AT)

How to cite

APA:

Pfeifle, R., Rothe, T., Ipseiz, N., Scherer, H.U., Culemann, S., Harre, U.,... Krönke, G. (2017). Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease. Nature Immunology, 18(1), 104-113. https://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: Download