A5052043095- Immune Cell Function and Interaction
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- T-cell and B-cell Immunology
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Signaling Pathways in Disease
- Ubiquitin and proteasome pathways
- vaccines and immunoinformatics approaches
- Glycosylation and Glycoproteins Research
- T-cell and Retrovirus Studies
- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- RNA Interference and Gene Delivery
- Sirtuins and Resveratrol in Medicine
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Cancer Research and Treatments
- Autophagy in Disease and Therapy
Centre National de la Recherche Scientifique
2015-2024
La Jolla Institute for Immunology
2023-2024
Institut de Génétique Moléculaire de Montpellier
2015-2024
Université de Montpellier
2015-2024
T cell activation requires that the meet increased energetic and biosynthetic demands. We showed exogenous nutrient availability regulated differentiation of naïve CD4(+) cells into distinct subsets. Activation under conditions glutamine deprivation resulted in their Foxp3(+) (forkhead box P3-positive) regulatory (Treg) cells, which had suppressor function vivo. Moreover, glutamine-deprived were activated presence cytokines normally induce generation helper 1 (TH1) instead differentiated...
Abstract CD4 and CD8 T lymphocyte activation requires the generation of sufficient energy to support new biosynthetic demands. Following cell receptor (TCR) engagement, these requirements are met by an increased glycolysis, due, at least in part, induction Glut1 glucose transporter. As is upregulated on tumor cells response hypoxia, we assessed whether surface levels regulate antigen responsiveness human lymphocytes both hypoxic atmospheric oxygen conditions. Notably, upregulation TCR...
Suppressive regulatory T cell (Treg) differentiation is controlled by diverse immunometabolic signaling pathways and intracellular metabolites. Here we show that cell-permeable α-ketoglutarate (αKG) alters the DNA methylation profile of naive CD4 cells activated under Treg polarizing conditions, markedly attenuating FoxP3+ increasing inflammatory cytokines. Adoptive transfer these into tumor-bearing mice results in enhanced tumor infiltration, decreased FoxP3 expression, delayed growth....
The 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 arrest G1 stage cell cycle, whereas low concentrations, were readily activated exhibited enhanced Sirt1 activity. Nevertheless, low-dose rapidly stimulated genotoxic stress cells, which resulted...
Abstract Both identity and plasticity of CD4 T helper (Th) cells are regulated in part by epigenetic mechanisms. However, a method that reliably readily profiles DNA base modifications is still needed to finely study Th cell differentiation. Cytosine methylation (5mC) cytosine hydroxymethylation (5hmC) identify stable phenotypes but their potential characterize intermediate transitions has not yet been evaluated. To assess transition states cells, we developed new profile using cas9-targeted...
Abstract Both identity and plasticity of CD4 T helper (Th) cells are regulated in part by epigenetic mechanisms. However, a method that reliably readily profiles DNA base modifications is still needed to finely study Th cell differentiation. Cytosine methylation CpG context (5mCpG) cytosine hydroxymethylation (5hmCpG) identify stable phenotypes, but their potential characterize intermediate transitions has not yet been evaluated. To assess transition states cells, we developed profile using...
<h3>Background</h3> CD8<sup>+</sup> T cells can infiltrate tumor tissues and target cells, but often fail to cure disease due chronic activation in the immunosuppressive microenvironment, resulting differentiation into an exhausted cell state. When acute infection is cleared tissues, pathogen-specific differentiate tissue-resident memory (T<sub>RM</sub>) that remain survey protect from reinfection. And when T<sub>RM</sub>-like TIL are found cancerous tissue, improved responses immunotherapy...
Abstract The differentiation of CD4 T cells to a specific effector fate is metabolically regulated, integrating glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) with transcriptional epigenetic changes. OXPHOS tightly coordinated the tricarboxylic acid (TCA) cycle but precise role TCA intermediates in cell remain unclear. Here we demonstrate that α-ketoglutarate (αKG) inhibited regulatory (Treg) generation while conversely, increasing Th1 polarization. In accord these data, αKG...
<h3>Background</h3> In malignancies, CD8<sup>+</sup> tumor-infiltrating lymphocytes (TIL) can target tumor cells, but often fail to cure disease due chronic TIL activation in the tissue's immunosuppressive microenvironment, resulting differentiation into an exhausted T cell state. healthy tissues, cells differentiate tissue-resident memory (T<sub>RM</sub>) response infection, and after clearance of antigen remain survey protect from reinfection. When T<sub>RM</sub>-like are found cancerous...
Abstract Signaling pathways that drive gene expression are typically depicted as having a dozen or so landmark phosphorylation and transcriptional events. In reality, thousands of dynamic post-translational modifications (PTMs) orchestrate nearly every cellular function, we lack technologies to find causal links between these vast biochemical genetic circuits at scale. Here, describe “signaling-to-transcription network” mapping through the development PTM-centric base editing coupled...
Suppressive regulatory T cell (Treg) differentiation is controlled by diverse immunometabolic signaling pathways. However, the impact of intracellular metabolites on Treg fate has not been well explored. Here we show that α-ketoglutarate (αKG) tricarboxylic acid (TCA) cycle metabolite increases oxidative phosphorylation (OXPHOS) in naïve CD4 cells activated under polarizing conditions, markedly attenuating Foxp3+ and increasing inflammatory cytokine expression. Adoptive transfer these into...