Editorial: Knocking on neuroimmunology’s doors: an entrechat concerning the immune system balance and its cell metabolism orchestration

ISSN:1664-322

Transert de gènes dans les lymphocytes T (de la thérapie génique à la "biologie" des cellules)

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Different conditioning protocols result in distinct lymphopenic environments: consequences for regulatory T cells and anti-tumor immunotherapy

Different conditioning protocols result in distinct lymphopenic environments: consequences for regulatory T cells and anti-tumor immunotherapy. ATTACK Cellular Therapy of Cancer Symposiu

Different conditioning protocols result in distinct lymphopenic environments: consequences for regulatory T cells and anti-tumor immunotherapy

Different conditioning protocols result in distinct lymphopenic environments: consequences for regulatory T cells and anti-tumor immunotherapy. Annual Meeting of the French Society for Immunolog

Different conditionning protocols result in distinct lymphopenic environments: consequences for anti-tumor immunotherapies

Different conditionning protocols result in distinct lymphopenic environments: consequences for anti-tumor immunotherapies. 18. Edition du Congrès Nantes/Actualités/Transplantation (N.A.T.

Cyclin G: looking for the causes of developmental noise

International audienceDrosophila melanogaster Cyclin G (dCycG) controls transcription and regulates the cell cycle. We previously determined that dCycG shares many transcriptional targets with the Polycomb PRC1 and PR-DUB complexes1. Overexpression of a potentially more stable form of dCycG down-regulates genes involved in mitochondrial activity. Interestingly, it also induces a high developmental noise, as estimated by an increase of wing fluctuating asymmetry (FA) in adults2. Overexpression of dCycG in background mutants for the Polycomb complexes PRC1 or PR-DUB leads to a previously unseen FA1. We show here that dCycG directly interacts with dRing, the ubiquitine-ligase of PRC1 and Calypso, the deubiquitinase of PR-DUB. Our resullts suggest that dCycG undergoes a ubiquitination/deubiquitination cycle driven by these complexes and bookmarks its transcriptional targets during mitosis. We have produced a dCycG mutant by CRISPR/Cas9. This mutant displays a high FA. Although its amount of mitochondrial DNA does not vary, wing imaginal disc respiration unexpectedly increases. The next step will be to check the amount of Reactive Oxygen Species in these tissues and address whether an increase in ROS is causal to developmental noise

Resveratrol stimulates the metabolic reprogramming of human CD4 + T cells to enhance effector function

International audienceThe polyphenol resveratrol activates the deacetylase Sirt1, resulting in various antioxidant, chemoprotectant, neuroprotective, cardioprotective, and anti-inflammatory properties. We found that at high concentrations of resveratrol, human CD4+ T cells showed defective antigen receptor signaling and arrest at the G1 stage of the cell cycle, whereas at low concentrations, cells were readily activated and exhibited enhanced Sirt1 deacetylase activity. Nevertheless, low-dose resveratrol rapidly stimulated genotoxic stress in the T cells, which resulted in engagement of a DNA damage response pathway that depended on the kinase ATR [ataxia telangiectasia–mutated (ATM) and Rad3-related], but not ATM, and subsequently in premitotic cell cycle arrest. The concomitant activation of p53 was coupled to the expression of gene products that regulate cell metabolism, leading to a metabolic reprogramming that was characterized by decreased glycolysis, increased glutamine consumption, and a shift to oxidative phosphorylation. These alterations in the bioenergetic homeostasis of CD4+ T cells resulted in enhanced effector function, with both naïve and memory CD4+ T cells secreting increased amounts of the inflammatory cytokine interferon-γ. Thus, our data highlight the wide range of metabolic adaptations that CD4+ T lymphocytes undergo in response to genomic stress

Entry of glucose- and glutamine-derived carbons into the citric acid cycle supports early steps of HIV-1 infection in CD4 T cells

International audienc

Single amino-acid mutation in a Drosoph ila melanogaster ribosomal protein: An insight in uL11 transcriptional activity.

The ribosomal protein uL11 is located at the basis of the ribosome P-stalk and plays a paramount role in translational efficiency. In addition, no mutant for uL11 is available suggesting that this gene is haplo-insufficient as many other Ribosomal Protein Genes (RPGs). We have previously shown that overexpression of Drosophila melanogaster uL11 enhances the transcription of many RPGs and Ribosomal Biogenesis genes (RiBis) suggesting that uL11 might globally regulate the level of translation through its transcriptional activity. Moreover, uL11 trimethylated on lysine 3 (uL11K3me3) interacts with the chromodomain of the Enhancer of Polycomb and Trithorax Corto, and both proteins co-localize with RNA Polymerase II at many sites on polytene chromosomes. These data have led to the hypothesis that the N-terminal end of uL11, and more particularly the trimethylation of lysine 3, supports the extra-ribosomal activity of uL11 in transcription. To address this question, we mutated the lysine 3 codon using a CRISPR/Cas9 strategy and obtained several lysine 3 mutants. We describe here the first mutants of D. melanogaster uL11. Unexpectedly, the uL11K3A mutant, in which the lysine 3 codon is replaced by an alanine, displays a genuine Minute phenotype known to be characteristic of RPG deletions (longer development, low fertility, high lethality, thin and short bristles) whereas the uL11K3Y mutant, in which the lysine 3 codon is replaced by a tyrosine, is unaffected. In agreement, the rate of translation decreases in uL11K3A but not in uL11K3Y. Co-immunoprecipitation experiments show that the interaction between uL11 and the Corto chromodomain is impaired by both mutations. However, Histone Association Assays indicate that the mutant proteins still bind chromatin. RNA-seq analyses from wing imaginal discs show that Corto represses RPG expression whereas very few genes are deregulated in uL11 mutants. We propose that Corto, by repressing RPG expression, ensures that all ribosomal proteins are present at the correct stoichiometry, and that uL11 fine-tunes its transcriptional regulation of RPGs