Institute of Development, Aging and Cancer, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
J Immunol. 2009 Dec 15;183(12):7817-24. doi: 10.4049/jimmunol.0802527.
Recently, it was reported that the expression of Runt-related transcription factor 3 (Runx3) is up-regulated in CD4(+) helper T cells during Th1 cell differentiation, and that Runx3 functions in a positive feed-forward manner with the T-box family transcription factor, T-bet, which is a master regulator of Th1 cell differentiation. The relative expression levels of IFN-gamma and IL-4 are also regulated by the Th2-associated transcription factor, GATA3. Here, we demonstrate that Runx3 was induced in Th2 as well as Th1 cells and that Runx3 interacted with GATA3 and attenuated GATA3 transcriptional activity. Ectopic expression of Runx3 in vitro in cultured cells or transgenic expression of Runx3 in mice accelerated CD4(+) cells to a Th1-biased population or down-modulated Th2 responses, in part by neutralizing GATA3. Our results suggest that the balance of Runx3 and GATA3 is one factor that influences the manifestation of CD4(+) cells as the Th1 or Th2 phenotypes.
最近有报道称，在 Th1 细胞分化过程中，Runt 相关转录因子 3（Runx3）在 CD4+辅助 T 细胞中的表达上调，并且 Runx3 与 T 盒家族转录因子 T-bet 以正反馈的方式发挥作用，T-bet 是 Th1 细胞分化的主调控因子。Th2 相关转录因子 GATA3 也调节 IFN-γ和 IL-4 的相对表达水平。在这里，我们证明 Runx3 在 Th2 和 Th1 细胞中均被诱导，并且 Runx3 与 GATA3 相互作用并减弱 GATA3 的转录活性。体外培养细胞中转染 Runx3 或在小鼠中过表达 Runx3 加速了 CD4+细胞向 Th1 偏向群体的转化，或下调 Th2 反应，部分是通过中和 GATA3。我们的结果表明，Runx3 和 GATA3 的平衡是影响 CD4+细胞表现为 Th1 或 Th2 表型的一个因素。
