title: 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 naïve 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 naïve CD4(+) T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro differentiation of naïve 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 differences from the Tregs generated in the absence of TSA. Thus, 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 differentiation and suppressive function of CD4(+)Foxp3(+) Treg cells.
authors.affiliation: Departamento de Ciencias Biológicas, Universidad Andrés Bello, República 275, Santiago, Chile.
authors.forename: Cristian
authors.initials: C
authors.lastname: Doñas
authors.forename: Macarena
authors.initials: M
authors.lastname: Fritz
authors.forename: Valeria
authors.initials: V
authors.lastname: Manríquez
authors.forename: Gabriela
authors.initials: G
authors.lastname: Tejón
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Bono
authors.forename: Alejandra
authors.initials: A
authors.lastname: Loyola
authors.forename: Mario
authors.initials: M
authors.lastname: Rosemblatt
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000276:immunology; D000107:Acetylation; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001081:Apyrase / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D049452:Green Fluorescent Proteins; C012589:trichostatin A; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen