Project description:The forkhead DNA-binding protein FOXP3 is critical for the development and suppressive function of CD4+CD25+ regulatory T cells (TREG), which play a key role in maintaining self tolerance. Functionally, FOXP3 is capable of repressing transcription of cytokine genes regulated by the Nuclear Factor of Activated T cells (NFAT). Various mechanisms have been proposed by which FOXP3 mediates these effects. Using novel HEK cell lines that inducibly express either wild-type (WT) or mutant FOXP3, we have identified genome-wide expression patterns showing among other features that NFAT2 as an early target of FOXP3-mediated transcriptional repression. Six biological replicates of wild-type induced FOXP3 cell lines and six biological replicates of mutated FOXP3 cell line were studied.
Project description:mRNA profiles of T cells from 8-week-old wild-type (Foxp3 YFP/cre) or Ebi3-KO (Foxp3 YFP/cre Ebi3-/-) mice were generated by 3'-sequencing, in triplicate.
Project description:Overexpressed either GFP, wild-type (WT) NFIX or a phospho-dead mutant of NFIX in which eight serine residues surrounding S286 were mutated to alanine (S265/267/268/271/272/273/274/275A) was performed C2C12 cells prior to the induction of myogenesis. Cells were harvest 2 days post induction of myogensis with 2% horse serum.
Project description:expression profile in Bcl11b-deficient Treg cells versus wild type Treg cells Treg cells sorted from Bcl11bF/F/Cd4Cre/Foxp3-GFP+ mice and wild type Foxp3-GFP+ mice Treg cells sorted from Bcl11bF/F/Foxp3Cre mice and wild type mice
Project description:mRNA profiles of CD8+ T cells from 8-week-old wild-type (Foxp3 YFP/cre) mice treated with control or leukemic sEV were generated by 3'-sequencing, in triplicate.
Project description:Gene expression of Treg cells that have lost Foxp3 expression and acquired Il4 expression following adoptive transfer into T-cell deficient mice (HpTR-IL-4gfp+), cmpared to conventional Treg cells isolated from H. polygyrus-infected wild-type mice (HpTR) and Th2 cells generated from naïve T cells following adoptive transfer into H. polygyrus-infected T-cell deficient mice (nT-IL-4gfp+). Immunity to intestinal helminth infections requires the rapid activation of T helper 2 (Th2) cells. However, simultaneous expansion of regulatory CD4+Foxp3+ T (Treg) cells impedes protective responses, resulting in chronic infections. The ratio between regulatory and effector T cells can therefore determine the outcome of infection. The re-differentiation of Treg into T helper (Th) cells has been identified in hyper-inflammatory diseases. In this study, we asked whether ex-Treg Th2 cells develop and contribute to type 2 immunity. Using multi-gene reporter and fate-reporter systems we demonstrate that a significant proportion of Th2 cells derive from Foxp3+ cells following Heligmosomoides polygyrus infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2 effector functions and provide immunity to H. polygyrus. Through selective deletion of Il4ra on Foxp3+ cells, we further demonstrate IL-4 is required for the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that converting Treg cells into Th2 cells could concomitantly enhance Th2 cells and limit Treg-mediated suppression.
Project description:Human CD4+CD45RA+CD25- cells were lentivirally transduced with wild-type or mutated (A384T or R397W) FOXP3, or an empty vector (EV). Transduced cells were sorted 14 days post-transduction based on GFP expression, and were restimulated with soluble anti-CD3 (30 ng/mL) and irradiated PBMCs (3x) for 14 more days. Cells were then activated with 0.5 μg/ml of phytohemagglutinin (PHA) in the presence or absence of SGF003 (8 μg/mL), and total RNA was extracted for microarray analysis. Overall, this study highlights the functional impact of TIP60 in FOXP3-driven Treg biology and provides a novel target for manipulation of human Treg activity. This study analyzes the transcriptional changes induced by the ectopic expression of FOXP3 in human effector T cells. It also assesses the impact of the enhancement of TIP60/FOXP3 interaction using the TIP60 modifier SGF003
Project description:expression profile in Bcl11b-deficient Treg cells versus wild type Treg cells Treg cells sorted from Bcl11bF/F/Cd4Cre/Foxp3-GFP+ mice and wild type Foxp3-GFP+ mice Treg cells sorted from Bcl11bF/F/Foxp3Cre mice and wild type mice RNA extracted from sorted Bcl11b-deficient Foxp3-GFP Treg cells form Bcl11bF/F/Cd4Cre/Foxp3-GFP+ mice and wild type Foxp3-GFP Treg cells; expression profile by microarray analysis RNA extracted from sorted Bcl11b-deficient Treg cells form Bcl11bF/F/Foxp3Cre mice and wild type Treg cells; expression profile by microarray analysis