白细胞介素2在Th2细胞分化中起核心作用。
Interleukin 2 plays a central role in Th2 differentiation.
作者信息
Cote-Sierra Javier, Foucras Gilles, Guo Liying, Chiodetti Lynda, Young Howard A, Hu-Li Jane, Zhu Jinfang, Paul William E
机构信息
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3880-5. doi: 10.1073/pnas.0400339101. Epub 2004 Mar 5.
Differentiation of naïve CD4 T cells into T helper (Th) 2 cells requires signaling through the T cell receptor and an appropriate cytokine environment. IL-4 is critical for such Th2 differentiation. We show that IL-2 plays a central role in this process. The effect of IL-2 on Th2 generation does not depend on its cell growth or survival effects. Stat5a(-/-) cells show diminished differentiation to IL-4 production, and forced expression of a constitutively active form of Stat5a replaces the need for IL-2. In vivo IL-2 neutralization inhibits IL-4 production in two models. Studies of restriction enzyme accessibility and binding of Stat5 to chromatin indicate that IL-2 mediates its effect by stabilizing the accessibility of the Il4 gene. Thus, IL-2 plays a critical role in the polarization of naive CD4 T cells to the Th2 phenotype.
初始CD4 T细胞分化为辅助性T细胞（Th）2细胞需要通过T细胞受体进行信号传导以及适宜的细胞因子环境。白细胞介素-4（IL-4）对于这种Th2分化至关重要。我们发现IL-2在此过程中发挥核心作用。IL-2对Th2细胞生成的影响并不依赖于其细胞生长或存活效应。Stat5a基因敲除（Stat5a(-/-)）细胞向IL-4产生的分化能力减弱，而强制表达组成型活性形式的Stat5a可替代对IL-2的需求。在体内，IL-2中和在两种模型中均抑制IL-4的产生。对限制酶可及性以及Stat5与染色质结合的研究表明，IL-2通过稳定Il4基因的可及性来介导其效应。因此，IL-2在初始CD4 T细胞向Th2表型的极化过程中发挥关键作用。
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