A5061582593- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- FOXO transcription factor regulation
- Cell death mechanisms and regulation
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Protein Kinase Regulation and GTPase Signaling
- Ion Channels and Receptors
- Autoimmune and Inflammatory Disorders Research
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Hematopoietic Stem Cell Transplantation
- RNA Research and Splicing
- Wnt/β-catenin signaling in development and cancer
- PARP inhibition in cancer therapy
- Herbal Medicine Research Studies
- Protein Tyrosine Phosphatases
- Lipid metabolism and biosynthesis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- interferon and immune responses
- Chemokine receptors and signaling
- Heat shock proteins research
Université de Strasbourg
2018-2024
Centre National de la Recherche Scientifique
2012-2024
Institut de génétique et de biologie moléculaire et cellulaire
2018-2024
Inserm
2002-2024
Université Paris Cité
2013-2018
Centre de Gestion Scientifique
2015-2018
Institut Cochin
2013-2018
Délégation Paris 5
2014-2018
Sorbonne Paris Cité
2015
Hôpital Cochin
2013
ABSTRACT Glycogen synthase kinase 3 (GSK-3) is involved in various signaling pathways controlling metabolism, differentiation and immunity, as well cell death survival. GSK-3 targets transcription factors, regulates the activity of metabolic enzymes, controls half-life proteins by earmarking them for degradation. unique its mode substrate recognition regulation activity, which repressed pro-survival phosphoinositide 3-kinase (PI3K)–AKT signaling. In turn, exhibits pro-apoptotic functions...
An uncontrolled exaggerated Th17 response can drive the onset of autoimmune and inflammatory diseases. In this study, we show that, in T cells, Foxo1 is a negative regulator program. Using mixed bone marrow chimeras Foxo1-deficient mice, demonstrate that control effective vivo, as well vitro during differentiation assays naive cells with specific inhibitor or inhibitors PI3K/Akt pathway acting upstream Foxo1. Consistently, expressing transcription factor strongly decreases generation both...
Methotrexate is the first line of treatment rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased tolerance strategies need be identified. Here we propose encapsulation in a new liposomal formulation using hydrophobic fragment surfactant protein conjugated linker folate enhance their efficacy. In this study aim evaluate efficiency system treat arthritis, by targeting receptor β present at...
Abstract Synthetic glucocorticoids (GC), such as dexamethasone, are extensively used to treat chronic inflammation and autoimmune disorders. However, long-term treatments limited by various side effects, including muscle atrophy. GC activities mediated the glucocorticoid receptor (GR), that regulates target gene expression in tissues association with cell-specific co-regulators. Here we show GR lysine-specific demethylase 1 (LSD1) interact myofibers of male mice, LSD1 connects GR-bound...
If misregulated, macrophage-T cell interactions can drive chronic inflammation thereby causing diseases, such as rheumatoid arthritis (RA). We report that in a proinflammatory environment, granulocyte-macrophage (GM-CSF)- and macrophage colony-stimulating factor (M-CSF)-dependent macrophages have dichotomous effects on T activity. While GM-CSF-dependent show highly stimulatory activity typical for M1 macrophages, M-CSF-dependent marked by folate receptor β (FRβ), adopt an immunosuppressive...
To better apprehend γ/δ T cell biological functions in the periphery, it appears crucial to identify markers highlighting existence of distinct phenotypic and functional subsets. Interestingly, expression CD44 Ly-6C subdivides murine peripheral cells into several subsets, with Ly-6C(-) CD44(hi) corresponding IL-17-producing CD27(-) subset exhibiting innate-like features. By comparing other subsets naive memory CD8(+) α/β cells, this study, we show that Ly-6C(- or +) CD44(lo) Ly-6C(+)CD44(hi)...
Abstract CD4 regulatory T cells (Tregs) can be subdivided into two subsets according to Ly-6C expression in the periphery. Phenotypic analysis, imaging, and adoptive-transfer experiments of peripheral Ly-6C− Ly-6C+ Tregs reveal that nonexpression by ∼70% depends on TCR signaling events. Interestingly, express higher surface amounts key immunosuppressive molecules than do produce constitutively anti-inflammatory cytokines. In line with their phenotype, exhibit poor suppressive capacities...
Foxo family transcription factors are critically involved in multiple processes, such as metabolism, quiescence, cell survival and differentiation. Although continuous, high activity of extends the life span some species, involvement proteins mammalian aging remains to be determined. Here, we show that Foxo1 is down-regulated with age mouse T cells. This down-regulation cells may contribute disruption naive T-cell homeostasis age, leading an increase number memory also associated...
Abstract Vav proteins play a critical role in T cell activation and proliferation by promoting cytoskeleton reorganization, transcription factor activation, cytokine production. In this study, we investigated the of cycle progression. TCR/CD28-stimulated Vav1−/− cells displayed block at G0-G1 stage, which accounted for their defective proliferation. This defect was associated with impaired TCR/CD28-induced phosphorylation Akt Forkhead family factor, FOXO1. The cytoplasmic localization FOXO1...
SWAP-70-like adapter of T cells (SLAT) is a novel guanine nucleotide exchange factor for Rho GTPases that upregulated in Th2 cells, but whose physiological function unclear. We show SLAT(-/-) mice displayed developmental defect at one the earliest stages thymocyte differentiation, double-negative 1 (DN1) stage, leading to decreased peripheral cell numbers. CD4(+) demonstrated impaired TCR/CD28-induced proliferation and IL-2 production, which was rescued by addition exogenous IL-2....
The Vav family of guanine exchange factors plays a critical role in lymphocyte proliferation, cytoskeletal reorganization, and gene transcription upon immunoreceptor engagement. Although the Vav1 T cells is well documented, Vav3 less clear. We investigated subcellular localization during cell activation. report here that phosphorylation on tyrosine residue Tyr(173) not required for receptor (TCR)-induced membrane translocation or immunological synapse (IS) recruitment, but mutation this...
Significance The production of proinflammatory cytokines, particularly granulocyte-macrophage colony-stimulating factor, by CD4 + T cells is a key process for amplifying immune responses but can also lead to harmful tissue damage in pathologies like multiple sclerosis and Covid-19. Correctly controlling the expression cytokines therefore major interest. However, pathogenic signature relies on transcriptional program that thus far poorly understood. Here, we identified transcription factor...
The Vav family of guanine nucleotide exchange factors for Rho GTPases plays a critical role in lymphocyte proliferation, gene transcription, and cytoskeleton reorganization following immunoreceptor stimulation. However, its immediate early activation is unclear. In this study, we have investigated the mechanisms by which Vav1 can regulate c-fos serum response element transcriptional activity. We show that T cell antigen receptor (TCR) stimulation induces phosphorylation factor (SRF) on...
Vav1 and Vav2 are members of the Dbl family guanine nucleotide exchange factors for Rho small GTPases. Although role during lymphocyte development activation is well characterized, function still unclear. In this study, we compared signaling pathways regulated by following engagement T cell receptor (TCR). We show that tyrosine-phosphorylated upon TCR stimulation co-expressed Src Syk kinases. Using glutathione S-transferase fusion proteins, observed homology 2 domain binds proteins from...
Protein kinase C theta (PKC theta) is unique among PKC isozymes in its translocation to the center of immune synapse T cells and downstream signaling. Here we show that hematopoietic protein tyrosine phosphatase (HePTP) also accumulates a theta-dependent manner upon antigen recognition by phosphorylated at Ser-225, which required for lipid raft translocation. Immune was completely absent antigen-specific from theta-/- mice. In intact cells, HePTP-S225A enhanced T-cell receptor (TCR)-induced...
SPATA2 mediates the recruitment of CYLD to immune receptor complexes by bridging interaction with linear ubiquitylation assembly complex (LUBAC) component HOIP. Whether exhibits functions independently is unclear. Here, we show that, while Cyld−/− and Spata2−/− mice are viable, double mutants exhibit highly penetrant perinatal lethality, indicating independent CYLD. Cyld−/−Spata2−/− fibroblasts increased M1-linked TNFR1-SC and, similar macrophages intestinal epithelial cells, elevated...
Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a widely used treatment for broad range of hematologic malignancies because its graft-versus-tumor (GVT) effect. Unfortunately, allo-HSCT still associated with morbidity and mortality related to relapse complications, namely graft-versus-host-disease (GVHD). In an era therapies specifically targeting molecular pathways, transcription factors, cytokines, better understanding GVHD physiopathology essential the development new...
Abstract Growth factor withdrawal induces rapid apoptosis via mitochondrial outer membrane permeabilization. We had previously observed that cell death of IL-3-dependent Ba/F3 cells, induced by removal the growth factor, required activity kinase GSK-3. Employing CRISPR/Cas9-mediated gene knockout, we aimed to identify pro-apoptotic GSK-3 regulated factors in this process. Knockout either Puma or Bim demonstrated induction , but not was crucial for IL-3 deprivation. Thus, at identifying...