Hsu HC, Yang P, Wang J et al.Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol 9:166-175

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Nature Immunology (Impact Factor: 20). 03/2008; 9(2):166-75. DOI: 10.1038/ni1552
Source: PubMed


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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    • "Likewise, patients with SLE have increased numbers of IL-17-producing cells and an elevated level of IL-17 in the serum, and IL-17-producing cells in affected kidneys (17, 24). It is possible that IL-17-producing cells, as opposed to other T-cell subsets, are early participants in mounting the immune response in peripheral lymphoid tissues (25, 26) and target organs in these patients. Recently, it has been shown that increased Th17 cells correlates with IFN type 1-inducible signature in SLE patients (27). "
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    Frontiers in Immunology 05/2014; 5:233. DOI:10.3389/fimmu.2014.00233
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    • "IL-23 inducing mucosal antibody responses is a novel observation and clearly further work is required to address the mechanism. Based on previous reports of IL-17 influencing B cell activation [31] and germinal center development [32], the IL-23 bearing CYT-IVAC could be modulating Th17 responses. Recently, activation of lung Th17 cells were also found to induce the development of polymeric Ig receptor and elevate mucosal secretion of IgA antibodies [33]. "
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    • "Interestingly, IL-21, a cytokine produced by Th17 cells, in combination with BAFF, has been reported to induce synergistically the differentiation of human memory B cells into antibody-producing plasma cells in the absence of further co-stimulation [25]. BAFF is known to be involved in germinal center formation [26], a process in which IL-17 is also involved [27]. "
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