Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
EMBO J. 2011 May 18;30(10):2071-82. doi: 10.1038/emboj.2011.111. Epub 2011 Apr 15.
Type 2 T helper (T(H)2) cells are critical for the development of allergic immune responses; however, the molecular mechanism controlling their effector function is still largely unclear. Here, we report that the transcription factor NFIL3/E4BP4 regulates cytokine production and effector function by T(H)2 cells. NFIL3 is highly expressed in T(H)2 cells but much less in T(H)1 cells. Production of interleukin (IL)-13 and IL-5 is significantly increased in Nfil3(-/-) T(H)2 cells and is decreased by expression of NFIL3 in wild-type T(H)2 cells. NFIL3 directly binds to and negatively regulates the Il13 gene. In contrast, IL-4 production is decreased in Nfil3(-/-) T(H)2 cells. Increased IL-13 and IL-5 together with decreased IL-4 production by antigen-stimulated splenocytes from the immunized Nfil3(-/-) mice was also observed. The ability of NFIL3 to alter T(H)2 cytokine production is a T-cell intrinsic effect. Taken together, these data indicate that NFIL3 is a key regulator of T(H)2 responses.
2 型 T 辅助细胞（T(H)2）对于过敏免疫反应的发展至关重要；然而，控制其效应功能的分子机制在很大程度上仍不清楚。在这里，我们报告转录因子 NFIL3/E4BP4 通过 T(H)2 细胞调节细胞因子的产生和效应功能。NFIL3 在 T(H)2 细胞中高度表达，而在 T(H)1 细胞中则表达较少。Nfil3(-/-)T(H)2 细胞中白细胞介素（IL）-13 和 IL-5 的产生显著增加，而野生型 T(H)2 细胞中 NFIL3 的表达则降低。NFIL3 直接结合并负调控 Il13 基因。相比之下，Nfil3(-/-)T(H)2 细胞中 IL-4 的产生减少。在免疫的 Nfil3(-/-)小鼠的抗原刺激脾细胞中，也观察到增加的 IL-13 和 IL-5 以及减少的 IL-4 产生。NFIL3 改变 T(H)2 细胞因子产生的能力是 T 细胞内在的效应。总之，这些数据表明 NFIL3 是 T(H)2 反应的关键调节因子。
