Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
J Immunol. 2014 Jun 15;192(12):5703-9. doi: 10.4049/jimmunol.1302830. Epub 2014 May 12.
Kruppel-like factor (KLF) 13 is a transcription factor that positively regulates expression of the chemokine RANTES 3-5 d after activation of T cells. In this study, we document a key role for KLF13 in the expression of IL-4 in CD4(+) T cells. Gene expression analysis in activated T cells from Klf13(-/-) mice showed that IL-4, along with other Th2 cytokine genes, was downregulated when compared with cells from wild-type mice. The decreased levels of IL-4 were not associated with changes in expression of the Th2-inducing transcription factors GATA3 or c-Maf. Additional analysis revealed that KLF13 directly binds to IL-4 promoter regions and synergizes with c-Maf to positively regulate IL-4 expression. These results indicate that KLF13 is a positive regulator for differentiation of Th2 cells, as part of the transcriptional machinery that regulates IL-4 production in Th2 cells.
Kruppel 样因子 (KLF) 13 是一种转录因子，可在 T 细胞活化后 3-5 天正向调节趋化因子 RANTES 的表达。在这项研究中，我们记录了 KLF13 在 CD4(+) T 细胞中 IL-4 表达中的关键作用。与野生型小鼠相比，从 Klf13(-/-) 小鼠激活的 T 细胞中的基因表达分析表明，IL-4 与其他 Th2 细胞因子基因一起下调。IL-4 水平的降低与 Th2 诱导转录因子 GATA3 或 c-Maf 的表达变化无关。进一步的分析表明，KLF13 直接与 IL-4 启动子区域结合，并与 c-Maf 协同正向调节 IL-4 的表达。这些结果表明，KLF13 是 Th2 细胞分化的正向调节因子，是调节 Th2 细胞中 IL-4 产生的转录机制的一部分。
