Li Bin, Greene Mark I
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Cell Cycle. 2007 Jun 15;6(12):1432-6. Epub 2007 May 10.
The Forkhead box protein P3 (FOXP3) is a master cell lineage modulator in CD4(+)CD25(+) natural regulatory T cell (Treg) development. The Treg set of cells, also called T suppressor cells, play an essential role in natural Treg-mediated suppression of various types of immune cells. Suppression can be manifest by a cell-cell contact set of events, and recent evidence also supports soluble mediators. FOXP3 was previous identified as a passive transcriptional repressor which associates with nuclear factor of activated T-cells, cytoplasmic, and calcineurin-dependent 2 (NFATc2) as well as several other transcriptional factors including nuclear factor kappa-B (NFkappaB) and acute myeloid leukemia 1(AML1)/runt-related transcription factor 1(RUNX1). We found FOXP3 could actively repress transcription by recruiting distinct histone acetyltransferases and histone deacetylases to function as a co-repressor complex. The identification of enzymatic factors operative as essential participants in FOXP3-mediated transcriptional repression provides a practical basis for therapeutically modulating the activity of FOXP3 in immune suppression. Here we briefly summarize recent progress in our understanding of the biochemistry of FOXP3-mediated transcriptional regulation.
叉头框蛋白P3（FOXP3）是CD4(+)CD25(+)自然调节性T细胞（Treg）发育过程中的主要细胞谱系调节因子。Treg细胞群，也称为T抑制细胞，在自然Treg介导的对各种免疫细胞的抑制中发挥着重要作用。抑制作用可通过一系列细胞间接触事件表现出来，最近的证据也支持可溶性介质的作用。FOXP3先前被鉴定为一种被动转录抑制因子，它与活化T细胞的核因子、细胞质和钙调神经磷酸酶依赖性2（NFATc2）以及其他几种转录因子相关，包括核因子κB（NFκB）和急性髓系白血病1（AML1）/ runt相关转录因子1（RUNX1）。我们发现FOXP3可以通过招募不同的组蛋白乙酰转移酶和组蛋白去乙酰化酶来作为共抑制复合物发挥作用，从而积极抑制转录。鉴定出作为FOXP3介导的转录抑制重要参与者的酶因子，为在免疫抑制中治疗性调节FOXP3的活性提供了实际依据。在此，我们简要总结了我们对FOXP3介导的转录调控生物化学理解的最新进展。
