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Interleukin 17–producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice

Open access
Hsu, Hui-Chen, Yang, PingAr, Wang, John, Wu, Qi, Myers, Riley, Chen, Jian, Yi, John, Guentert, Tanja, Tousson, Albert, Stanus, Andrea L, Le, Thuc-vy L, Lorenz, Robin G, Xu, Hui, Kolls, Jay K, Carter, Robert H, Chaplin, David D, Williams, Robert W, Mountz, John D·2008·Nature Immunology

Abstract

Interleukin 17 (IL-17) is a cytokine associated with inflammation, autoimmunity and defense against some bacteria. Here we show that IL-17 can promote autoimmune disease through a mechanism distinct from its proinflammatory effects. As compared with wild-type mice, autoimmune BXD2 mice express more IL-17 and show spontaneous development of germinal centers (GCs) before they increase production of pathogenic autoantibodies. We show that blocking IL-17 signaling disrupts CD4+ T cell and B cell interactions required for the formation of GCs and that mice lacking the IL-17 receptor have reduced GC B cell development and humoral responses. Production of IL-17 correlates with upregulated expression of the genes Rgs13 and Rgs16, which encode regulators of G-protein signaling, and results in suppression of the B cell chemotactic response to the chemokine CXCL12. These findings suggest a mechanism by which IL-17 drives autoimmune responses by promoting the formation of spontaneous GCs.

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Metadata

Authors
Hsu, H.-C., Yang, P., Wang, J., Wu, Q., Myers, R., Chen, J., Yi, J., Guentert, T., Tousson, A., Stanus, A. L., Le, T.-V. L., Lorenz, R. G., Xu, H., Kolls, J. K., Carter, R. H., Chaplin, D. D., Williams, R. W., & Mountz, J. D.
Venue
Nature Immunology
Published
2007-12-23
Volume
9
Issue
2
Pages
166-175
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2171571685
Cited by
716
References
4
FWCI
18.32
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Interleukin 17–producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. https://app.cochat.ai/papers/10.1038/ni1552
The paper
Hsu, H.-C., Yang, P., Wang, J., Wu, Q., Myers, R., Chen, J., Yi, J., Guentert, T., Tousson, A., Stanus, A. L., Le, T.-V. L., Lorenz, R. G., Xu, H., Kolls, J. K., Carter, R. H., Chaplin, D. D., Williams, R. W., & Mountz, J. D. (2008). Interleukin 17–producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nature Immunology. https://doi.org/10.1038/ni1552

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.