The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-γ production
The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-γ production
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DOI：
10.1002/eji.200838575
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发表时间：
2009-04-01
影响因子：
5.4
通讯作者：
Herbelin, Andre
中科院分区：
文献类型：
--
作者：
Bourgeois, Elvire;Van, Linh Pham;Herbelin, Andre
IL-33最近被确定为一种具有Th2前功能的细胞因子，这引发了它对具有强大的IL-4产生能力的不变自然杀伤T细胞(INKT)的影响的问题。在这里，我们报道了用IL-33治疗小鼠7天后，小鼠脾和肝脏中的iNKT细胞数量增加了两倍，这是直接作用的结果，因为纯化的iNKT细胞表达T1/ST2受体，并通过体外扩增和功能激活对IL-33做出反应。相反，与预期的Th2前效应相反，IL-33通过依赖内源性IL-12的TCR参与，优先诱导干扰素-γ而不是IL-4的产生。此外，与促炎细胞因子IL-12相结合，IL-33可促进iNKT和NK细胞产生干扰素-γ。综上所述，这些数据支持了这样的结论，即IL-33可以作为一种共刺激因子对先天细胞免疫反应做出贡献。
IL-33 has recently been identified as a cytokine endowed with pro-Th2 functions, raising the question of its effect on invariant natural killer T cell (iNKT), which are potent IL-4 producers. Here, we report a two-fold increase of iNKT-cell counts in spleen and liver after a 7-day treatment of mice with IL-33, which results from a direct effect, given that purified iNKT cells express the T1/ST2 receptor constitutively and respond to IL-33 by in vitro expansion and functional activation. Conversely to the expected pro-Th2 effect, IL-33 induced a preferential increase in IFN-gamma rather than IL-4 production upon TCR engagement that depended on endogenous IL-12. Moreover, in combination with the pro-inflammatory cytokine IL-12, IL-33 enhanced IFN-gamma production by both iNKT and NK cells. Taken together these data support the conclusion that IL-33 can contribute as a co-stimulatory factor to innate cellular immune responses.