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

Pfeifle, R., Rothe, T., Ipseiz, N. ORCID: https://orcid.org/0000-0001-5008-8889, Scherer, H.U., Culemann, S., Harre, U., Ackermann, J.A., Seefried, M., Kleyer, A., Uderhardt, S., Haugg, B., Hueber, A.J., Daum, P., Heidkamp, G.F., Ge, C., Bohm, S., Lux, A., Schuh, W., Magorivska, I., Nandakumar, K.S., Lonnblom, E., Becker, C., Dudziak, D., Wuhrer, M., Rombouts, Y., Koeleman, C.A., Toes, R., Winkler, T.H., Holmdahl, R., Herrmann, M., Bluml, S., Nimmerjahn, F., Schett, G. and Kronke, G. 2016. 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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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.

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 08:30
URI: https://orca.cardiff.ac.uk/id/eprint/127669

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