A5060760269- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Mast cells and histamine
- Phagocytosis and Immune Regulation
- Lymphoma Diagnosis and Treatment
- Glycosylation and Glycoproteins Research
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Galectins and Cancer Biology
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- HER2/EGFR in Cancer Research
- Immunodeficiency and Autoimmune Disorders
- Platelet Disorders and Treatments
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Wnt/β-catenin signaling in development and cancer
- Cellular transport and secretion
- Kruppel-like factors research
- Pancreatic function and diabetes
- Cancer-related gene regulation
- PI3K/AKT/mTOR signaling in cancer
- Systemic Sclerosis and Related Diseases
- Immunotherapy and Immune Responses
Equipe de Recherche en Epidémiologie Nutritionnelle
2009-2024
Inserm
2014-2024
Université Sorbonne Paris Nord
2014-2024
Sorbonne Université
2010-2022
Sorbonne Paris Cité
2011-2022
Université Paris Cité
2007-2022
Association pour la Recherche en Physiologie de l’Environnement
2011-2021
Adaptateurs de Signalisation en Hématologie
2010-2015
Institut Curie
1988-2015
Assistance Publique – Hôpitaux de Paris
2012
To define functionally critical regions of the high affinity receptor for IgE (Fc epsilon RI), we stably transfected P815 cells with mutated cDNAs coding subunits truncated cytoplasmic domains (CD). In addition, to examine further role beta subunit, stable transfectants expressing chimeric Fc RI without were generated. Transfectants tested receptor-mediated changes in intracellular Ca2+, stimulated hydrolysis phosphoinositides, and protein tyrosine phosphorylation. all cases these...
Compound exocytosis of inflammatory mediators from mast cells requires SNARE and a series accessory proteins. However, the molecular steps that regulate secretory granule movement membrane fusion as well role cytoskeleton are still poorly understood. Here, we report on our investigation syntaxin-binding Munc18 isoforms microtubule network in this process. We found express Munc18-2, which interacts with target SNAREs syntaxin 2 or 3, Munc18-3, 4. Munc18-2 was localised to granules, whereas...
To study the role of B lymphocytes in systemic sclerosis (SSc).Peripheral cell subpopulations and production interleukin-6 (IL-6) transforming growth factor β (TGFβ) were analyzed using flow cytometry multiplex assay. The fibroblast proliferation rate upon incubation with supernatants from cells isolated SSc patients or healthy controls was assessed XTT, bromodeoxyuridine, Ki-67. Collagen a collagen assay.Ninety untreated (12 males) fulfilling American College Rheumatology/European League...
Abstract Despite very similar gene expression profiles, the clinical course of B-cell chronic lymphocytic leukemia (B-CLL) is heterogeneous. Immunoglobulin VH (IgVH) mutational status and receptor (BCR) signaling mediators have been associated with disease progression. However, consequences BCR engagement on cell survival evolution remain unclear. We show here that B-CLL dependent threshold stimulation induced by immobilized antibody, in contrast to soluble anti-μ F(ab)′2 which leads...
Progressive cases of B-cell chronic lymphocytic leukemia (CLL) are frequently associated with lymphadenopathy, highlighting a critical role for signals emanating from the tumor environment in accumulation malignant B cells. We investigated on CLL cells 30 untreated patients consequence receptor (BCR) triggering membrane expression CXCR4 and CD62L, two surface molecules involved trafficking exit B-lymphocytes lymph nodes. BCR stimulation promoted strictly simultaneous down-regulation CD62L to...
Abstract Mast cell degranulation requires N-ethylmaleimide–sensitive factor attachment protein receptors (SNARE) and mammalian uncoordinated18 (Munc18) fusion accessory proteins for membrane fusion. However, it is still unknown how their interaction supports In this study, we found that small interfering RNA–mediated silencing of the isoform Munc18-2 in mast cells inhibits cytoplasmic secretory granule (SG) release but not CCL2 chemokine secretion. Silencing its SNARE-binding partner...
The deregulation of several transcription factors contribute to the aggressive course mantle cell lymphoma. This study focuses on survival signals emanating from tumor environment and involving signal transducer activator (STAT) 3 through cytokines or antigen recognition.Primary lymphoma cells were isolated 20 leukemic patients. phosphorylation status STAT3 was evaluated by immunoblottting immunofluorescence, levels cytokine secretion enzyme-linked immunosorbent assay apoptosis viability...
The endoplasmic reticulum (ER) is a major intracellular calcium storage pool and multifunctional organelle that accomplishes several calcium-dependent functions involved in many homeostatic signaling mechanisms. Calcium accumulated the ER by Sarco/Endoplasmic Reticulum ATPase (SERCA)-type pumps. SERCA activity can determine content available for intra-ER release into cytosol, shape spatiotemporal characteristics of signals. function therefore constitutes an important nodal point regulation...
Abstract Background The transcription factor STAT3 (signal transducer and activator of 3) is frequently activated in tumor cells. Activated forms homodimers, or heterodimers with other TFs such as NF-κB, which becomes activated. Cytoplasmic dimers are by tyrosine phosphorylation; they interact importins via a nuclear localization signal (NLS) one located within the DNA-binding domain formed dimer. In nucleus, regulates target gene expression binding consensus sequence promoter....
Background Interactions with the microenvironment, such as bone marrow mesenchymal stromal cells and nurse-like cells, protect chronic lymphocytic leukemia from spontaneous drug-induced apoptosis. This protection is partially mediated by chemokine SDF-1α (CXCL12) its receptor CXCR4 (CD184) present on cell surface.Design Methods Here, we investigated ability of AMD3100, a antagonist, to sensitize chemotherapy in leukemia/mesenchymal based or microenvironment co-culture model.Results AMD3100...
Several studies provide evidences for mantle cell lymphoma (MCL) survival relying on B-cell receptor (BCR)-mediated signalling pathways, whereas the nature of this activation is unknown. Significant progress in MCL treatment achieved through therapies targeting BCR-associated kinases, i.e., Ibrutinib and Fostamatinib, inhibitors BTK SYK, respectively. Our study addresses signals emanating from BCR or tumour environment how inhibiting effectors might impact these signals. We found that was...
The importance of the hematopoietic protooncogene Vav1 in immune cell function is widely recognized, although its regulatory mechanisms are not completely understood. Here, we examined whether has a nuclear function, as past studies have reported localization. Our findings provide definitive demonstration localization receptor stimulation–dependent manner and reveal critical role for COOH-terminal Src homology 3 (SH3) domain sequence within pleckstrin domain. Analysis DNA-bound transcription...
The mast cell receptor with high affinity for IgE consists of four transmembrane polypeptides which are held together by detergent-sensitive interactions: an IgE-binding alpha chain, a single beta and disulfide-linked dimer gamma chains. Now that the cDNAs code each subunits have been isolated, it should be possible to probe site-specific mutations, portions critical signaling. One prerequisite such studies is mutant receptors expressible on surface. We explored this issue transiently...
Abstract The problem of the structural relationship between suppressive IgG‐binding factor and low‐affinity receptors for Fc portion IgG (FcγRII) has not yet been solved. In present work we have isolated a recombinant soluble FcγRII containing only two external domains FcγRII, analyzed its biochemical characteristics biological activity. A cDNA encoding was mutated by creation stop codon at Lys 175 codon. L cells transfected with this inserted into an expression vector. cell line obtained...
Abstract Technological developments of multiparametric flow cytometry come along with the generation new dyes. The APC‐tandem dyes, which combine fluorophores APC and Cy7/H7, allow detection a specific signal in APC‐Cy7/H7 channel an unexpected nonspecific channel. Depending on magnitude latter, it may be handicap for interpreting data multicolor labeling experiments. We investigated alteration dyes by peripheral blood cells antibodies directed toward leukocyte surface proteins analyzing...
Abstract Background The Signal Transducer and Activator of Transcription 3 (STAT3) is activated in tumor cells, STAT3-inhibitors are able to induce the death those cells. Decoy oligodeoxynucleotides (dODNs), which bind DNA Binding Domain (DBD) STAT3, efficient inhibitors. However, they also inhibit STAT1, whose activity essential not only resistance pathogens, but cell growth inhibition programmed processes. aim this study was design STAT3-specific dODNs do affect STAT1-mediated Results New...
Tumor microenvironment exerts a critical role in sustaining homing, retention, and survival of chronic lymphocytic leukemia (CLL) cells secondary lymphoid organs. Such conditions foster immune surveillance escape resistance to therapies. The physiological is rendered tumor permissive by an interplay chemokines, chemokine receptors, adhesion molecules as well direct interactions between malignant lymphocytes stromal cells, T specialized macrophages referred nurselike (NLCs). To characterize...
Chronic Lymphocytic Leukemia (CLL) is a heterogeneous B cell neoplasm ranging from indolent to rapidly progressive disease. Leukemic subsets with regulatory properties evade immune clearance; however, the contribution of such during CLL progression not completely elucidated. Here, we report that cells crosstalk their counterparts, notably by promoting T (Treg) compartment and shaping several helper (Th) subsets. Among various constitutively- BCR/CD40-mediated factors secreted, tumour...