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

HC Hsu, PA Yang, J Wang, Q Wu, R Myers, J Chen… - Nature …, 2008 - nature.com
HC Hsu, PA Yang, J Wang, Q Wu, R Myers, J Chen, J Yi, T Guentert, A Tousson, AL Stanus…
Nature immunology, 2008nature.com
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 …
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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