Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice.
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.
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17