Induction of IL-4 expression in CD4+ T cells by thymic stromal lymphopoietin

Induction of IL-4 expression in CD4+ T cells by thymic stromal lymphopoietin
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DOI:
10.4049/jimmunol.178.3.1396
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发表时间:
2007-02-01
影响因子:
4.4
通讯作者:
Ziegler, Steven
Ziegler, Steven
中科院分区:
医学2区
文献类型:
--
作者:
Omori, Miyuki;Ziegler, Steven

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细胞因子胸腺基质淋巴生成素(TSLP)与人类和小鼠过敏性炎症的发生和进展有关。虽然潜在的机制尚不清楚,但tslp刺激的树突状细胞已被证明可将人CD4(+) T细胞转化为Th2细胞因子产生细胞。然而,其对CD4(+) T细胞的直接作用尚未被广泛研究。在这项研究中,我们发现TSLP可以在缺乏外源IL-4和apc的情况下驱动Th2分化。IL-4阻断抑制了tslp介导的Th2分化,表明IL-4参与了这一过程。进一步的分析表明,TSLP诱导的Th2分化依赖于Stat6而不依赖于IL-2,并且TSLP处理会导致11-4基因的直接转录。综上所述,这些数据表明TSLP通过诱导IL-4的产生直接参与了th2介导的应答。
The cytokine thymic stromal lymphopoietin (TSLP) has been implicated in the development and progression of allergic inflammation in both humans and mice. Although the underlying mechanism is not known, TSLP-stimulated dendritic cells have been shown to prime human CD4(+) T cells into Th2 cytokine-producing cells. However, its direct effect on CD4(+) T cells has not been extensively investigated. In this study, we show that TSLP can drive Th2 differentiation in the absence of exogenous IL-4 and APCs. IL-4 blockade inhibited TSLP-mediated Th2 differentiation, demonstrating that IL-4 is involved in this process. Further analysis has shown that TSLP-induced Th2 differentiation is dependent on Stat6 and independent of IL-2 and that TSLP treatment leads to immediate, direct 11-4 gene transcription. Taken together, these data demonstrate that TSLP is directly involved in Th2-mediated responses via the induction of IL-4 production.