Omori Miyuki, Ziegler Steven
Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA.
J Immunol. 2007 Feb 1;178(3):1396-404. doi: 10.4049/jimmunol.178.3.1396.
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 Il-4 gene transcription. Taken together, these data demonstrate that TSLP is directly involved in Th2-mediated responses via the induction of IL-4 production.
细胞因子胸腺基质淋巴细胞生成素（TSLP）与人类和小鼠过敏性炎症的发生发展有关。尽管其潜在机制尚不清楚，但已表明TSLP刺激的树突状细胞可将人CD4(+) T细胞诱导分化为产生Th2细胞因子的细胞。然而，其对CD4(+) T细胞的直接作用尚未得到广泛研究。在本研究中，我们发现TSLP在无外源性IL-4和抗原呈递细胞（APC）的情况下可驱动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。进一步分析表明，TSLP诱导的Th2分化依赖于Stat6且不依赖于IL-2，并且TSLP处理可导致IL-4基因立即直接转录。综上所述，这些数据表明TSLP通过诱导IL-4产生直接参与Th2介导的反应。
