Article abstract
Nature Immunology 9, 166 - 175 (2007)
Published online: 23 December 2007 | doi:10.1038/ni1552
Interleukin 17–producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice
Hui-Chen Hsu1, PingAr Yang1, John Wang1, Qi Wu1, Riley Myers1, Jian Chen1, John Yi2, Tanja Guentert1, Albert Tousson3, Andrea L Stanus4, Thuc-vy L Le2, Robin G Lorenz4, Hui Xu5, Jay K Kolls6, Robert H Carter1,7, David D Chaplin2, Robert W Williams8 & John D Mountz1,7
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.
- Departments of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Dermatology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Pediatric Pulmonology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
- Birmingham VA Medical Center, Birmingham, Alabama 35233, USA.
- Department of Anatomy and Neurobiology, University of Tennessee at Memphis, Memphis, Tennessee 38152, USA.
Correspondence to: Hui-Chen Hsu1 e-mail: huichen.hsu@ccc.uab.edu
Correspondence to: John D Mountz1,7 e-mail: john.mountz@ccc.uab.edu
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