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, 9 (2), 166-75

Interleukin 17-producing T Helper Cells and Interleukin 17 Orchestrate Autoreactive Germinal Center Development in Autoimmune BXD2 Mice

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Interleukin 17-producing T Helper Cells and Interleukin 17 Orchestrate Autoreactive Germinal Center Development in Autoimmune BXD2 Mice

Hui-Chen Hsu et al. Nat Immunol.

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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