Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Curr Opin Immunol. 2010 Oct;22(5):583-91. doi: 10.1016/j.coi.2010.08.013. Epub 2010 Sep 24.
Regulatory T cells (Tregs) are required for the maintenance of immune homeostasis as first clearly described by Herman Waldmann's laboratory. Dysfunction of Treg cells also leads to fatal autoimmunity in humans and mice. Conversely, the activation of different classes of Tregs operative systemically and within the cancer microenvironment can suppress host anti-tumor immune responses and promote tumor progression. Therefore, the development of new therapeutic approaches to regulate the activity of Treg cells may have considerable clinical potential. FOXP3 is the key transcriptional regulator of Treg development and function. The activity of FOXP3 is regulated by acetylation, a process catalyzed by distinct types of histone/protein acetyltransferases (HATs) that regulate the functions of many transcription factors, independently of FOXP3, as well as non-histone proteins, in addition to their effects on chromatin accessibility. Interactions between FOXP3 and these enzymes determine the suppressive function of FOXP3. Clearly, small molecules targeting these enzymes are candidates for the regulation of Treg function in vaccines and tumor therapies.
调节性 T 细胞（Tregs）对于维持免疫稳态是必需的，这首先由赫尔曼·沃尔德曼（Herman Waldmann）的实验室明确描述。Treg 细胞的功能障碍也会导致人类和小鼠的致命自身免疫。相反，在全身和肿瘤微环境中发挥作用的不同类别的 Tregs 的激活可以抑制宿主抗肿瘤免疫反应并促进肿瘤进展。因此，开发新的治疗方法来调节 Treg 细胞的活性可能具有相当大的临床潜力。FOXP3 是 Treg 发育和功能的关键转录调节因子。FOXP3 的活性受乙酰化调节，该过程由不同类型的组蛋白/蛋白乙酰转移酶（HATs）催化，这些酶独立于 FOXP3 调节许多转录因子的功能，以及除了它们对染色质可及性的影响之外，还调节非组蛋白蛋白的功能。FOXP3 与这些酶之间的相互作用决定了 FOXP3 的抑制功能。显然，针对这些酶的小分子是调节疫苗和肿瘤治疗中 Treg 功能的候选药物。
