NFIL3/E4BP4 controls type 2 T helper cell cytokine expression
NFIL3/E4BP4 controls type 2 T helper cell cytokine expression
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DOI：
10.1038/emboj.2011.111
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发表时间：
2011-05-18
期刊：
影响因子：
11.4
通讯作者：
Rothman, Paul B.
中科院分区：
文献类型：
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作者：
Kashiwada, Masaki;Cassel, Suzanne L.;Rothman, Paul B.
2型辅助性T细胞（T（H）2）对过敏性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仍不清楚。在这里，我们报告了转录因子NFIL 3/E4 BP 4调节T（H）2细胞的细胞因子产生和效应子功能。NFIL 3在T（H）2细胞中高度表达，但在T（H）1细胞中低得多。在Nfil 3（-/-）T（H）2细胞中，白细胞介素（IL）-13和IL-5的产生显著增加，而在野生型T（H）2细胞中，Nfil 3的表达降低了白细胞介素（IL）-13和IL-5的产生。NFIL 3直接结合并负调控Il 13基因。相反，IL-4的产生在Nfil 3（-/-）T（H）2细胞中减少。还观察到来自免疫的Nfil 3（-/-）小鼠的抗原刺激的脾细胞产生的IL-13和IL-5增加以及IL-4减少。NFIL 3改变T（H）2细胞因子产生的能力是T细胞内在效应。总之，这些数据表明NFIL 3是T（H）2应答的关键调节因子。The EMBO Journal（2011）30，2071-2082. doi：10.1038/daj.2011.111; 2011年4月15日在线发布
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. The EMBO Journal (2011) 30, 2071-2082. doi: 10.1038/emboj.2011.111; Published online 15 April 2011