Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2013, Article ID 679804, 8 pages http://dx.doi.org/10.1155/2013/679804 Research Article Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells Cristian Doñas, 1,2 Macarena Fritz, 1,2 Valeria Manríquez, 3 Gabriela Tejón, 3 María Rosa Bono, 3 Alejandra Loyola, 2,4 and Mario Rosemblatt 1,2,3 1 Departamento de Ciencias Biol´ ogicas, Universidad Andr´ es Bello, Rep´ ublica 275, Santiago, Chile 2 Fundaci´ on Ciencia & Vida, Avenida Za˜ nartu 1482, ˜ Nu˜ noa, Santiago, Chile 3 Laboratorio de Inmunolog´ ıa, Departamento de Biolog´ ıa, Facultad de Ciencias, Las Palmeras 3425, ˜ Nu˜ noa, Universidad de Chile, Santiago, Chile 4 Universidad San Sebasti´ an, Avenida Lota 2465, Providencia, Santiago, Chile Correspondence should be addressed to Mario Rosemblatt; mrosemblatt@cienciavida.cl Received 30 January 2013; Revised 9 April 2013; Accepted 9 April 2013 Academic Editor: Nicolaus Kroger Copyright © 2013 Cristian Do˜ nas et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Regulatory T cells are a speciic subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. hey can be generated in the thymus as well as in the periphery through diferentiation of na¨ ıve CD4 + T cells. he 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 diferentiated Tregs compared to na¨ ıve CD4 + T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro diferentiation 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 of TSA have phenotypical and functional diferences from the Tregs generated in the absence of TSA. hus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the diferentiation and suppressive function of CD4 + Foxp3 + Treg cells. 1. Introduction Regulatory T cells (Treg) are a speciic subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance [1, 2]. heir development and function are programmed by the forkhead box P3 transcription factor Foxp3, which is predominantly expressed in CD4 + CD25 + Treg cells [1, 3]. Tregs actively suppress the activation and expansion of autoreactive immune cells to limit the duration and extent of inlammation. herefore, a decrease in Treg activity can contribute to autoimmunity and inlammatory diseases [4]. Because of their suppressive capacities, Tregs represent a promising strategy for inducing tolerance to self- and non-self-antigens in such diseases. In recent years, increasing evidence has demonstrated the role of epigenetic alterations in the etiology of many autoimmune and inlammatory diseases through changes in DNA methylation and histone modiications [5, 6]. herefore, it is important to determine crucial histone modiications for Treg development and function and to study compounds able to revert or modify epigenetic patterns. Among histones modiications is acetylation, which occurs at lysine residues mainly on their amino-terminal tails. his posttranslational modiication is dynamic and its overall efect on gene expression depends on the balance between histone acetyltransferases (HATs) and histone deacetylases (HDACs) [7, 8]. HDACs typically dampen histone-DNA and histone-non histone protein interactions [9, 10], but they also regulate the function of non-histone proteins [11]. Histone deacetylase inhibitors (HDACi) such as tricho- statin A (TSA) are small molecule compounds capable of inhibiting class I, II, and IV HDAC families of enzymes [12].