A5038873652- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune cells in cancer
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- Galectins and Cancer Biology
- Single-cell and spatial transcriptomics
- Phagocytosis and Immune Regulation
- Chromosomal and Genetic Variations
- Axon Guidance and Neuronal Signaling
- Listeria monocytogenes in Food Safety
- Receptor Mechanisms and Signaling
- Signaling Pathways in Disease
- Cytokine Signaling Pathways and Interactions
- Viral Infectious Diseases and Gene Expression in Insects
- Fungal and yeast genetics research
- Inflammasome and immune disorders
- Systemic Lupus Erythematosus Research
- Protein Kinase Regulation and GTPase Signaling
- Biomarkers in Disease Mechanisms
- NF-κB Signaling Pathways
- Extracellular vesicles in disease
University of Oxford
2018-2025
Kennedy Center
2019-2023
Institute of Rheumatology
2019
University of California, San Francisco
2011-2018
Inserm
1991-2010
Institut Paoli-Calmettes
2009-2010
Centre de Recherche en Cancérologie de Marseille
2009-2010
Institut de Neurobiologie de la Méditerranée
2009-2010
The Netherlands Cancer Institute
2007-2009
Centre National de la Recherche Scientifique
1991
During immune surveillance, T cells survey the surface of antigen-presenting cells. In searching for peptide-loaded major histocompatibility complexes (pMHCs), they must solve a classic trade-off between speed and sensitivity. It has long been supposed that microvilli on act as sensory organs to enable search, but their strategy unknown. We used lattice light-sheet quantum dot-enabled synaptic contact mapping microscopy show anomalous diffusion fractal organization majority opposing surfaces...
Abstract IFNγ is an immune mediator with concomitant pro- and anti-tumor functions. Here, we provide evidence that directly acts on intra-tumoral CD8 T cells to restrict responses. We report expression of the receptor β chain (IFNγR2) in negatively correlates clinical responsiveness checkpoint blockade metastatic melanoma patients, suggesting loss sensitivity contributes successful antitumor immunity. Indeed, specific deletion IFNγR promotes tumor control a mouse model melanoma. Chronic...
Cell polarization is required for virtually all functions of T cells, including transendothelial migration in response to chemokines. However, the molecular pathways that establish cell polarity are poorly understood. We show activation partitioning defective (Par) complex a key event during Rap1- and chemokine-induced polarization. Intracellular localization Par initiated by Rap1 require Cdc42 activity. The Rac activator Tiam1 associates with both components complex, thereby may function...
The priming of immune T cells by their interaction with dendritic (DCs) in lymph nodes (LN), one the early events productive adaptive responses, occurs on a scaffold lymphoid stromal cells, which have largely been seen as support or sources chemokines and homeostatic growth factors. Here we show that murine fibroblastic reticular (FRCs), isolated from LN B6 mice, play more direct role response sensing modulating cell activation through upregulation inducible nitric oxide synthase (iNOS) to...
Abstract Loss of IFNγ-sensitivity by tumours is thought to be a mechanism enabling evasion, but recent studies suggest that IFNγ-resistant can sensitised for immunotherapy, yet the underlying remains unclear. Here, we show IFNγ receptor-deficient B16-F10 mouse melanoma are controlled as efficiently WT despite their lower MHC class I expression. Mechanistically, receptor deletion in increases availability, triggering remodelling immune landscape characterised inflammatory monocyte...
The cytokine IFN-γ is a critical regulator of immune system development and function. Almost all leukocytes express the receptor for IFN-γ, yet each cell type elicits different response to this cytokine. Cell type-specific effects make it difficult predict outcomes systemic blockade limit its clinical application, despite many years research. To better understand cell-cell interactions cofactors that specify functions, we focused on function CD8 T differentiation. We demonstrated during...
Abstract Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How selected throughout the response retain breadth of avidities remains unclear. Here, we demonstrate that direct sensing cytokine IFN-γ CD8 + cells coordinates avidity differentiation during infection. promotes expansion low-avidity cells, allowing them overcome selective advantage high-avidity whilst reinforcing...
Abstract Semaphorin-3A (SEMA3A) functions as a chemorepulsive signal during development and can affect T cells by altering their filamentous actin (F-actin) cytoskeleton. The exact extent of these effects on tumour-specific are not completely understood. Here we demonstrate that Neuropilin-1 (NRP1) Plexin-A1 Plexin-A4 upregulated stimulated CD8 + cells, allowing tumour-derived SEMA3A to inhibit cell migration assembly the immunological synapse. Deletion NRP1 in both CD4 enhance T-cell...
Downstream of tyrosine kinase (Dok) proteins Dok-1 and Dok-2 are involved in T cell homeostasis maintenance. Dok protein phosphorylation plays a key role establishing negative feedback loops signaling. These structurally related adapter molecules contain pleckstrin homology (PH) domain generally acting as lipid/protein-interacting module. We show that the presence this PH is necessary for their functions cells. find Dok-1/Dok-2 domains bind vitro to rare phosphoinositide species,...
Abstract T cells use the cell antigen receptor (TCR) to discriminate between higher-affinity foreign and lower-affinity self peptide-MHC (pMHC) antigens. The OT-I mouse TCR is widely used study anti-gen discrimination utilising many pMHCs, including Previous studies sug-gested that achieve near-perfect higher lower affinity Moreover, these 3D affinities measured in solution did not correlate with 2D membrane affinities, suggesting a complex relationship affinities. In contrast, other TCRs...
<title>Abstract</title> Resolution of inflammation, including colitis, requires carefully coordinated communication between different tissues. While the role immune cells in colitis is well established, less known about epithelial to its microenvironment. Most secreted factors that comprise cellular are directly regulated by transcription factor NF-κB. However, which transcriptomes NF-κB regulates epithelium during progression and whether these exacerbate or protect from remains...
Abstract The OX40-OX40L pathway provides crucial co-stimulatory signals for CD4 T cell responses, however the precise cellular interactions critical OX40L provision in vivo and when these occur, remains unclear. Here, we demonstrate that of by dendritic cells (DCs), but not cells, B nor group 3 innate lymphoid (ILC3s), is specifically effector Th1 response to an acute systemic infection with Listeria monocytogenes (Lm). expression DCs regulated cross-talk NK IFNγ signalling DC enhance a...
Phosphatidylinositol 5‐phosphate (PtdIns5P) is emerging as a potential lipid messenger involved in several cell types, from plants to mammals. Expression of IpgD, PtdIns(4, 5)P 2 4‐phosphatase induces Src kinase and Akt, but not ERK activation enhances interleukin II promoter activity T‐cells. new PtdIns5P interacting domain blocks IpgD‐induced T‐cell selective signaling molecules downstream TCR triggering. Altogether, these data suggest that may play sensor function setting the threshold...