A5035878821- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- CAR-T cell therapy research
- Immune cells in cancer
- 3D Printing in Biomedical Research
- Immune Response and Inflammation
- Cell Image Analysis Techniques
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Surface Modification and Superhydrophobicity
- RNA Interference and Gene Delivery
- NF-κB Signaling Pathways
- Caveolin-1 and cellular processes
- Micro and Nano Robotics
- Agriculture and Rural Development Research
- Rangeland Management and Livestock Ecology
- Blood properties and coagulation
- Ubiquitin and proteasome pathways
- Single-cell and spatial transcriptomics
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- interferon and immune responses
Inserm
2016-2025
Université Paris Sciences et Lettres
2016-2025
Institut Curie
2016-2025
Immunité et Cancer
2010-2025
Institut Pasteur
2010-2017
Centre National de la Recherche Scientifique
2017
Sorbonne Paris Cité
2012-2015
Université Paris Cité
2012-2015
Délégation Paris 7
2012-2015
École Normale Supérieure
2013
Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These can adapt to such deformation events using dedicated shape-sensing pathways. However, how sensing affects immune function is mostly unknown. Here, we identify a mechanism increases expression chemokine receptor CCR7 and guides dendritic migration from peripheral tissues lymph nodes at steady state. This relies on lipid...
Significance To mount an efficient immune response, T cells need to recognize foreign antigen become activated, proliferate, and acquire their effector functions. We show that can adopt two behaviors depending on the strength of stimulation. Upon suboptimal stimulation, a scanning behavior promotes local exploration microenvironment. Stronger stimulation triggers specific mechanisms induce complete T-cell arrest. propose these distinct may represent optimal strategy for find strongest antigenic
Dendritic cells (DCs) patrol tissues and transport antigens to lymph nodes initiate adaptive immune responses. Within tissues, DCs constitute a complex cell population composed of distinct subsets that can exhibit different activation states functions. How tissue-specific cues orchestrate DC diversification remains elusive. Here, we show the small intestine included two pools cDC2s originating from common pre-DC precursors: (1) lamina propria (LP) CD103
Contraction is a critical phase of immunity whereby the vast majority effector T cells die by apoptosis, sparing population long-lived memory cells. Where, when, and why contraction occurs has been difficult to address directly due in large part rapid clearance apoptotic vivo. To circumvent this issue, we introduced genetically encoded reporter for caspase-3 activity into naive identify entering phase. Using two-photon imaging, found that was maximal at peak response associated with loss...
Abstract During tumorigenesis, the extracellular matrix (ECM), which constitutes structural scaffold of tissues, is profoundly remodeled. While impact such remodeling on tumor growth and invasion has been extensively investigated, much less known consequences ECM infiltration by immune cells. By combining tissue imaging machine-learning, we here show that localization T lymphocytes neutrophils, orchestrate antitumor responses, can be predicted defined topographical features fibrillar...
Effector T cell responses rely on a phenotypically and functionally heterogeneous population of cells. Whether this diversity is programmed before clonal expansion or in later phases as result stochastic events asymmetric division not fully understood. In study, we first took advantage sensitive vitro assay to analyze the composition single CD8(+) progenies. Heterogeneity was predominantly observed between progenies distinct clones, but could also be detected within individual Furthermore,...
Dendritic cell (DC) trafficking from peripheral tissues to lymph nodes is a key step required initiate T responses against pathogens as well tumors. In this context, cellular membrane protrusions and the actin cytoskeleton are essential guide DC migration towards chemotactic signals. Caveolin-1 scaffolding protein that modulates signaling pathways leading remodeling of enhanced cancer cells. However, whether caveolin-1 relevant for function specifically unknown. Here we show expression...
Targeting TLR3 through formulations of polyI:C is widely studied as an adjuvant in cancer immunotherapy. The efficacy such targeting has been shown to increase combination with anti-PD-L1 treatment. Nevertheless, the mechanistic details effect on DC maturation and impact T-DC interactions upon PD-L1 blockade largely unknown. Here we found that although treatment induced a potent inflammatory response including production type I interferon, DCs impaired activation peptide specific CD8+ T...
The initiation of T-cell responses in lymph nodes requires T cells to integrate signals delivered by dendritic (DCs) during long-lasting contacts (synapses) or more transient interactions (kinapses). However, it remains extremely challenging understand how a specific sequence established ultimately dictates fate. Here, we have coupled computational model migration and with DCs real-time, flow cytometry-like representation activation. In this model, low-affinity peptides trigger proliferation...
Abstract Motile cells such as immune and cancer experience large deformation events that result from the physical constraints they encounter while migrating within tissues or circulating between organs. It has become increasingly clear these can survive adapt to changes in cell shape using dedicated sensing pathways. However, how impacts their function fate remains largely unknown. Here we identify a mechanism couples motility expression of CCR7, chemokine receptor guides lymph nodes. We...
Abstract Cell polarity is an essential and highly conserved process governing cell function. polarization generally triggered by external signal that induces the relocation of centrosome, thus defining axis cell. Here, we took advantage B cells as a model to study perform medium-throughput siRNA-based imaging screen identify new molecular regulators polarization. We first identified candidates based on quantitative proteomic analysis proteins differentially associated with centrosome resting...
Abstract Dendritic cells (DCs) devoid of the actin regulator Wiskott-Aldrich syndrome protein (WASp) show reduced directed migration and decreased formation podosome adhesion structures. We examined DCs expressing a gain-of-function mutation in WASp, WASp L272P, identified X-linked neutropenia patients. Analysis L272P was compared to WASp-deficient examine how activity influences DC migratory responses. In confined space, had increased speed whereas similar average but fluctuations,...
Dynamic in situ cytometry (DISC) is a new approach that combines advantages of both intravital imaging and flow analysis. The DISC methodology provides the opportunity to link cell behavior phenotype vivo hence perform real-time. In addition it enables you readily display analyze multiparametric data. Through concrete examples, we present guide experiments with help custom designed DISCit software.
Summary The migration of immune cells is guided by specific chemical signals, such as chemokine gradients. Their trajectories can also be diverted physical cues and obstacles imposed the cellular environment, topography, rigidity, adhesion, or hydraulic resistance. On example resistance, it was shown that neutrophil preferentially follow paths least a phenomenon referred to barotaxis. We here combined quantitative imaging modeling show barotaxis results from force imbalance at scale cell,...
Abstract The forces exerted by cells upon the fibers of extracellular matrix play a decisive role in cell motility development and disease. How local physical properties (such as density, stiffness, orientation) affect cellular remains poorly understood. Existing approaches to measure 3D traction within fibrous substrates lack control over rely on continuum approaches, not suited for measuring at scale individual fibers. A novel approach is proposed here fabricate multilayer arrays...