Interferon regulatory factor 4 differentially regulates the production of Th2 cytokines in naive vs. effector/memory CD4+ T cells
Interferon regulatory factor 4 differentially regulates the production of Th2 cytokines in naive vs. effector/memory CD4+ T cells
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DOI：
10.1073/pnas.0803171105
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发表时间：
2008-10-14
影响因子：
11.1
通讯作者：
Yui, Katsuyuki
中科院分区：
文献类型：
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作者：
Honma, Kiri;Kimura, Daisuke;Yui, Katsuyuki
干扰素调节因子 (IRF) 4 是 IRF 转录因子家族的成员，在 CD4(+) T 细胞发育为 Th2 和 Th17 细胞的过程中发挥着关键作用。利用巴西尼波圆线虫感染模型，我们通过IRF-4(-/-) BALB/c小鼠证实了IRF-4在体内Th2发育中的关键作用。然而，初始IRF-4(-/-)CD4(+) T细胞响应T细胞受体刺激，产生Th2细胞因子，包括IL-4、IL-5和IL-10，但不产生IL-2或IFN-γ，其水平高于野生型BALB/c CD4(+) T细胞。相反，效应/记忆IRF-4(-/-)CD4(+) T细胞没有表现出Th2细胞因子的产生增加。使用小干扰RNA敲低IRF-4表达可促进初始CD4(+) T细胞中IL-4的产生，但抑制效应/记忆CD4(+) T细胞中的IL-4产生。这些结果表明IRF-4在调节幼稚CD4(+)T细胞和效应/记忆CD4(+)T细胞的Th2细胞因子产生中发挥着不同的作用。 IRF-4抑制初始CD4(+)T细胞中Th2细胞因子的产生，而促进效应/记忆CD4(+)T细胞中Th2细胞因子的产生。
Interferon regulatory factor (IRF) 4 is a member of the IRF family of transcription factors and plays critical roles in the development of CD4(+) T cells into Th2 and Th17 cells. Using the infection model of Nippostrongyrus brasiliensis, we have confirmed the critical roles of IRF-4 in Th2 development in vivo by using IRF-4(-/-) BALB/c mice. However, naive IRF-4(-/-)CD4(+) T cells produced Th2 cytokines, including IL-4, IL-5, and IL-10, but not IL-2 or IFN-gamma, at levels higher than wild-type BALB/c CD4(+) T cells in response to T cell receptor stimulation. In contrast, effector/memory IRF-4(-/-)CD4(+) T cells did not exhibit increased production of Th2 cytokines. Knockdown of IRF-4 expression by using small interfering RNA promoted IL-4 production in naive CD4(+) T cells but inhibited it in effector/memory CD4(+) T cells. These results indicate that IRF-4 plays differential roles in the regulation of Th2 cytokine production in naive CD4(+) T cells and effector/memory CD4(+) T cells. IRF-4 inhibits Th2 cytokine production in naive CD4(+) T cells, whereas it promotes Th2 cytokine production in effector/memory CD4(+) T cells.