Histone acetyltransferase mediated regulation of FOXP3 acetylation and Treg function

Regulatory T cells (Tregs) are required for the maintenance of immune homeostasis as first clearly described by Herman Waldmann s laboratory Dysfunction of Treg cell, 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 cell, 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 nonhistone 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