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 g/ml of phytohemagglutinin (PHA) in the presence or absence of SGF003 (8 g/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.
Suppression by human FOXP3<sup>+</sup> regulatory T cells requires FOXP3-TIP60 interactions.
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View SamplesLoss of Pggt1b leads to marked defects in thymocyte egress and T cell lymphopenia in peripheral lymphoid organs in vivo
Mevalonate metabolism-dependent protein geranylgeranylation regulates thymocyte egress.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hippo/Mst signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions.
Specimen part, Disease
View SamplesMyelopoiesis is impaired in Raptor-deleted mice (CreER-Rptor-flox/flox). To evaluate the transcriptional changes in myeloid precursors , we isolated CMP (LinSca-1c-Kit+CD34+FcRII/IIImid), GMP (LinSca-1c-Kit+CD34+FcRII/IIIhigh) and Lin (B220, Ly6C, Ly6G, CD3, Ter-119) negative cells (Lin) from bone marrow of WT or CreER-Rptor-flox/flox mice. RNA was isolated from CMP and GMP immediately after sorting and Lin- cells were cultured for 12 hours with M-CSF (10 ng/mL) in 10% FBS and 1% P/S DMEM before RNA isolation.
Critical roles of mTORC1 signaling and metabolic reprogramming for M-CSF-mediated myelopoiesis.
Sex
View SamplesCD8+ DCs play key role in CD8+ T cell priming, however, the underlying signaling mechansim is unclear. We used a data-driven network-based systems biology approach and identified Hippo signaling kinases as key selective modualtors in CD8+ DCs. We focused on Mst1/Stk4 to further investigate the novel function of Hippo signaling in CD8+ DCs. All transcriptional profies were evalated by microarray.
Hippo/Mst signalling couples metabolic state and immune function of CD8α<sup>+</sup> dendritic cells.
Specimen part
View SamplesAmino acids license Treg cell function by priming and sustaining TCR induced mTORC1 activity and Rag and Rheb GTPases as central regulators of mTORC1 activation in effector Treg (eTreg) cells
Amino Acids License Kinase mTORC1 Activity and Treg Cell Function via Small G Proteins Rag and Rheb.
Specimen part, Treatment
View SamplesCD8+ T cells can be reprogrammed for better persistence and robust effector function in TME. By performing an in vivo pooled CRISPR-Cas9 mutagenesis screening of metabolism-associated factors, we identify Regnase-1 as a major negative regulator of antitumor responses, whose deficiency results in drastically increased CD8+ T cell accumulation in tumors
Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy.
Specimen part
View SamplesRegulatory T (Treg) cell activation and expansion during neonatal life and in response to inflammation are critical for immunosuppression, yet the mechanisms governing these events are incompletely understood. We report that the oncogene and transcriptional regulator c-Myc (Myc) controls immune homeostasis through regulation of Treg cell accumulation and functional activation. Myc activity is enriched in Treg cells generated during neonatal life and responding to inflammation. Myc-deficient Treg cells show cell-intrinsic defects in overall accumulation and ability to transition to an activated state during early life or acute inflammation. Consequently, loss of Myc in Treg cells results in a rapid, early-onset autoimmune disorder accompanied by uncontrolled effector CD4+ and CD8+ T cell responses. We also provide evidence that Myc regulates mitochondrial oxidative metabolism but is dispensable for fatty acid oxidation (FAO). Indeed, Treg cell-specific deletion of Cox10, which is required for oxidative phosphorylation, but not Cpt1a, the rate-limiting enzyme for FAO, results in impaired Treg cell function and maturation. Thus, Myc coordinates Treg cell accumulation, transitional activation and metabolic programming to orchestrate immune homeostasis.
Homeostasis and transitional activation of regulatory T cells require c-Myc.
Specimen part
View SamplesThe edible mushroom Agaricus blazei Murill has immunomodulating and antiproliferative effects. In a clinical study 33 patients with multiple myeloma were randomized to receive treatment with Agaricus (16 patients) or placebo (17 patients) in addition to chemotherapy.
Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.
Specimen part, Treatment, Subject, Time
View SamplesCytokine-induced signal transduction is executed by natural biological switches, which among many others control immune related processes. To construct a biological device, that simulates cytokine signaling, we utilized nanobodies to generate synthetic cytokine receptors (SyCyR). High affinity GFP- and mCherry-nanobodies were selected and extracellularly fused to trans-membrane and intracellular domains of IL-23 cytokine receptors. Soluble homo- and heterodimeric GFP:mCherry fusion proteins served as SyCyR ligands. Heterodimeric GFP-mCherry and homodimeric GFP fusion proteins efficiently phenocopied IL-23 signal transduction, respectively, as demonstrated by STAT3-, ERK- and Akt-activation, SOCS3 expression and transcriptome profiling. Interestingly, the homodimeric GFP fusion protein induced IL-23 receptor homo-dimerization and activation of IL-23-like signal transduction
Synthetic cytokine receptors transmit biological signals using artificial ligands.
Specimen part, Cell line
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