title: Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice.
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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. huichen.hsu@ccc.uab.edu
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Hsu
authors.forename: PingAr
authors.initials: P
authors.lastname: Yang
authors.forename: John
authors.initials: J
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Riley
authors.initials: R
authors.lastname: Myers
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Yi
authors.forename: Tanja
authors.initials: T
authors.lastname: Guentert
authors.forename: Albert
authors.initials: A
authors.lastname: Tousson
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Stanus
authors.forename: Thuc-vy L
authors.initials: TV
authors.lastname: Le
authors.forename: Robin G
authors.initials: RG
authors.lastname: Lorenz
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Robert H
authors.initials: RH
authors.lastname: Carter
authors.forename: David D
authors.initials: DD
authors.lastname: Chaplin
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.forename: John D
authors.initials: JD
authors.lastname: Mountz
mesh_terms: 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*
chemical_list: C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17