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

Hui Chen Hsu, Ping Ar Yang, John Wang, Qi Wu, Riley Myers, Jian Chen, John Yi, Tanja Guentert, Albert Tousson, Andrea L. Stanus, Thuc Vy L. Le, Robin G. Lorenz, Hui Xu, Jay K. Kolls, R. H.Robert H. Carter, David D. Chaplin, Robert Williams, John D. Mountz

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)166-175
Number of pages10
JournalNature Immunology
Volume9
Issue number2
DOIs
StatePublished - Feb 1 2008

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Germinal Center
Interleukin-17
Helper-Inducer T-Lymphocytes
B-Lymphocytes
Autoimmunity
Interleukin-17 Receptors
GTP-Binding Protein Regulators
Chemokine CXCL12
Cell Communication
Autoantibodies
Autoimmune Diseases
Cytokines
Inflammation
Bacteria
T-Lymphocytes
Gene Expression

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. / Hsu, Hui Chen; Yang, Ping Ar; 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, R. H.Robert H.; Chaplin, David D.; Williams, Robert; Mountz, John D.

In: Nature Immunology, Vol. 9, No. 2, 01.02.2008, p. 166-175.

Research output: Contribution to journalArticle

Hsu, HC, Yang, PA, Wang, J, Wu, Q, Myers, R, Chen, J, Yi, J, Guentert, T, Tousson, A, Stanus, AL, Le, TVL, Lorenz, RG, Xu, H, Kolls, JK, Carter, RHRH, Chaplin, DD, Williams, R & Mountz, JD 2008, 'Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice', Nature Immunology, vol. 9, no. 2, pp. 166-175. https://doi.org/10.1038/ni1552
Hsu, Hui Chen ; Yang, Ping Ar ; 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, R. H.Robert H. ; Chaplin, David D. ; Williams, Robert ; Mountz, John D. / Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. In: Nature Immunology. 2008 ; Vol. 9, No. 2. pp. 166-175.
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