Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice
Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice
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DOI：
10.1038/ni1552
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发表时间：
2008-02-01
影响因子：
30.5
通讯作者：
Mountz, John D.
中科院分区：
文献类型：
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作者：
Hsu, Hui-Chen;Yang, PingAr;Mountz, John D.
白细胞介素17（IL-17）是一种与炎症、自身免疫和抵抗某些细菌相关的细胞因子。在这里，我们表明，IL-17可以促进自身免疫性疾病，通过一种不同于其促炎作用的机制。与野生型小鼠相比，自身免疫BXD 2小鼠表达更多的IL-17，并在增加致病性自身抗体的产生之前显示出自发的生发中心（GC）发育。我们发现，阻断IL-17信号传导破坏了GC形成所需的CD 4（+）T细胞和B细胞的相互作用，缺乏IL-17受体的小鼠GC B细胞发育和体液应答减少。IL-17的产生与基因Rgs 13和Rgs 16的上调表达相关，所述基因Rgs 13和Rgs 16编码G蛋白信号传导的调节剂，并导致对趋化因子CXCL 12的B细胞趋化反应的抑制。这些发现表明IL-17通过促进自发GC的形成来驱动自身免疫应答的机制。
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.