Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells

Abstract

Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of na¨ıve CD4+ T cells. The forkhead box P3 transcription factor (Foxp3) is a crucial molecule regulating the generation and function of Tregs. Here we show that the foxp3 gene promoter becomes hyperacetylated in in vitro differentiated Tregs compared to na¨ıve CD4+ T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro differentiation of na¨ıve CD4+ T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence ofTSAhave phenotypical and functional differences fromtheTregs generated in the absence ofTSA.Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidasesCD39 and CD73.Our data showthat TSAcould potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+ Treg cells.