title: Analysis of the transcriptional program of developing induced regulatory T cells.
abstract: CD25+ regulatory T cells develop in the thymus (nTregs), but may also be generated in the periphery upon stimulation of naive CD4 T cells under appropriate conditions (iTregs). To gain insight into the mechanisms governing iTreg development, we performed longitudinal transcriptional profiling of CD25+ T cells during their differentiation from uncommitted naive CD4 T cells. Microarray analysis of mRNA from CD25+ iTregs early after stimulation revealed expression of genes involved in cell cycle progression and T cell activation, which largely overlapped with genes expressed in CD25+ effector T cells (Teffs) used as a control. Whereas expression of these genes remained elevated in Teffs, it declined gradually in developing iTregs, resulting in a more quiescent phenotype in mature iTregs. A similar pattern of kinetics was observed for biological processes and for intracellular pathways over-represented within the expressed genes. A maximum dichotomy of transcriptional activity between iTregs and Teffs was reached at late stages of their maturation. Of interest, members of the FoxO and FoxM1 transcription factor family pathways exhibited a reciprocal expression pattern in iTregs and Teffs, suggesting a role of these transcription factors in determining T cell fate.
authors.affiliation: Division of Rheumatology, Medizinische Poliklinik, University of Munich, Munich, Germany.
authors.forename: Iryna
authors.initials: I
authors.lastname: Prots
authors.forename: Alla
authors.initials: A
authors.lastname: Skapenko
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schulze-Koops
mesh_terms: D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D015847:Interleukin-4