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3 results on '"Florent Creusat"'

1. Modeling the crosstalk between malignant B cells and their microenvironment in B-cell lymphomas: challenges and opportunities

Author

Baptiste Brauge, Elise Dessauge, Florent Creusat, and Karin Tarte

Subjects
tumor microenvironment, follicular lymphoma, diffuse large B-cell lymphoma, germinal center, stromal cells, 3D models, Immunologic diseases. Allergy, RC581-607
Abstract

B-cell lymphomas are a group of heterogeneous neoplasms resulting from the clonal expansion of mature B cells arrested at various stages of differentiation. Specifically, two lymphoma subtypes arise from germinal centers (GCs), namely follicular lymphoma (FL) and GC B-cell diffuse large B-cell lymphoma (GCB-DLBCL). In addition to recent advances in describing the genetic landscape of FL and GCB-DLBCL, tumor microenvironment (TME) has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, and late progression/transformation. The lymphoma-supportive niche integrates a dynamic and coordinated network of immune and stromal cells defining microarchitecture and mechanical constraints and regulating tumor cell migration, survival, proliferation, and immune escape. Several questions are still unsolved regarding the interplay between lymphoma B cells and their TME, including the mechanisms supporting these bidirectional interactions, the impact of the kinetic and spatial heterogeneity of the tumor niche on B-cell heterogeneity, and how individual genetic alterations can trigger both B-cell intrinsic and B-cell extrinsic signals driving the reprogramming of non-malignant cells. Finally, it is not clear whether these interactions might promote resistance to treatment or, conversely, offer valuable therapeutic opportunities. A major challenge in addressing these questions is the lack of relevant models integrating tumor cells with specific genetic hits, non-malignant cells with adequate functional properties and organization, extracellular matrix, and biomechanical forces. We propose here an overview of the 3D in vitro models, xenograft approaches, and genetically-engineered mouse models recently developed to study GC B-cell lymphomas with a specific focus on the pros and cons of each strategy in understanding B-cell lymphomagenesis and evaluating new therapeutic strategies.

Published
2023
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2. Beneficial effects of citrulline enteral administration on sepsis-induced T cell mitochondrial dysfunction

Author

Florian Reizine, Murielle Grégoire, Mathieu Lesouhaitier, Valentin Coirier, Juliette Gauthier, Céline Delaloy, Elise Dessauge, Florent Creusat, Fabrice Uhel, Arnaud Gacouin, Frédéric Dessauge, Cécile Le Naoures, Caroline Moreau, Claude Bendavid, Yoann Daniel, Kilian Petitjean, Valérie Bordeau, Claire Lamaison, Caroline Piau, Vincent Cattoir, Mikael Roussel, Bernard Fromenty, Christian Michelet, Yves Le Tulzo, Jaroslaw Zmijewski, Ronan Thibault, Michel Cogné, Karin Tarte, Jean-Marc Tadié, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Etablissement Français du Sang Bretagne, EFS, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ARN régulateurs bactériens et médecine (BRM), Centre National de Référence de la Résistance aux Antibiotiques [CHU Rennes] (CNR), University of Alabama at Birmingham [ Birmingham] (UAB), This work was supported by funding from the Société de Réanimation de Langue Française (SRLF, Bourses Master 2 SRLF). We also thank the animal house Animalerie Rennaise Centre d’Hébergement et d’Expérimentation (ARCHE) platform and H2P2 platform (Structure Fédérative de Recherche [SFR] Biosit), and Aude Bodin for her help with mitochondrial functions analysis., Jonchère, Laurent, and Center of Experimental and Molecular Medicine

Subjects
Immunosuppression Therapy, Multidisciplinary, Myeloid-Derived Suppressor Cells, T-Lymphocytes, [SDV]Life Sciences [q-bio], Biological Availability, T cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Arginine, Lymphocyte Activation, T-Lymphocytes, Regulatory, Mitochondria, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], Disease Models, Animal, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, Sepsis, Immune Tolerance, Animals, Cytokines, Citrulline, Female
Abstract

International audience; Severe sepsis induces a sustained immune dysfunction associated with poor clinical behavior. In particular, lymphopenia along with increased lymphocyte apoptosis and decreased lymphocyte proliferation, enhanced circulating regulatory T cells (Treg), and the emergence of myeloid-derived suppressor cells (MDSCs) have all been associated with persistent organ dysfunction, secondary infections, and late mortality. The mechanisms involved in MDSC-mediated T cell dysfunction during sepsis share some features with those described in malignancies such as arginine deprivation. We hypothesized that increasing arginine availability would restore T cell function and decrease sepsis-induced immunosuppression. Using a mouse model of sepsis based on cecal ligation and puncture and secondary pneumonia triggered by methicillin-resistant Staphylococcus aureus inoculation, we demonstrated that citrulline administration was more efficient than arginine in increasing arginine plasma levels and restoring T cell mitochondrial function and proliferation while reducing sepsis-induced Treg and MDSC expansion. Because there is no specific therapeutic strategy to restore immune function after sepsis, we believe that our study provides evidence for developing citrulline-based clinical studies in sepsis.

Published
2022

3. Interleukin-7 protects against bacterial respiratory infection by promoting IL-17A-producing innate T-cell response

Author

Chloé Boisseau, Nathalie Heuzé-Vourc'h, Daphnée Soulard, François Trottein, Maya Hassane, Mustapha Si-Tahar, Loïc Gonzalez, Christelle Faveeuw, Thomas Baranek, Emmanuel C. Patin, Jean-Claude Sirard, Youenn Jouan, Christophe Paget, Florent Creusat, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), This work was funded with support by the Région Centre-Val de Loire under the program 'ARD 2020 Biomédicaments' (Project 7UP and Primine) and by the French Higher Education and Research ministry under the program 'Investissements d’avenir': LabEx MAbImprove (ANR-10-LABX-53-01). Y.J., N.H-V., J.C.S., C.F., M.Si-T., and C.P. are supported by Inserm. F.T. is supported by CNRS. T.B., L.G., and C.B. are supported by the University of Tours. D.S. is supported by the Pasteur Institute of Lille. M.H. was the recipient of a doctoral fellowship from the AZM foundation. Y.J. was the recipient of the 'Antoine RABBAT' doctoral fellowship from the 'Fonds de Recherche en Santé Respiratoire' under the support of the 'Fondation du Souffle'. E.C.P. was supported by a postdoctoral fellowship from the French Institute of cancer (INCa)., We also thank the Pasteur Institute of Lille and University of Tours animal facilities for excellent mouse husbanding. We thank the NIH tetramer core facility (Emory University) for providing CD1d and MR1 tetramers. The MR1:5-OP-RU tetramer technology was developed jointly by J. McCluskey, J. Rossjohn, and D. Fairlie, and the material was produced by the NIH Tetramer Core Facility as permitted to be distributed by the University of Melbourne., Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), TROTTEIN, François, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], and Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 [CEPR]

Subjects
0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Neutrophils, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Galactosylceramides, Pneumococcal Infections, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunity, RAR-related orphan receptor gamma, medicine, Animals, Humans, Immunology and Allergy, Antibodies, Blocking, Respiratory Tract Infections, Cells, Cultured, Mice, Knockout, biology, Interleukin-7, Interleukin-17, Interleukin, Nuclear Receptor Subfamily 1, Group F, Member 3, Immunity, Innate, Neutrophilia, 3. Good health, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Streptococcus pneumoniae, 030104 developmental biology, Cytokine, biology.protein, Natural Killer T-Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, Antibody, medicine.symptom, Homeostasis, 030215 immunology
Abstract

International audience; Interleukin-7 (IL-7) is a critical cytokine in B- and T-lymphocyte development and maturation. Recent evidence suggests that IL-7 is a preferential homeostatic and survival factor for RORγt+ innate T cells such as natural killer T (NKT) cells, γδT cells, and mucosal-associated invariant T (MAIT) cells in the periphery. Given the important contribution of these populations in antibacterial immunity at barrier sites, we questioned whether IL-7 could be instrumental in boosting the local host immune response against respiratory bacterial infection. By using a cytokine-monoclonal antibody approach, we illustrated a role for topical IL-7 delivery in increasing the pool of RORγt+ IL-17A-producing innate T cells. Prophylactic IL-7 treatment prior to Streptococcus pneumoniae infection led to better bacterial containment, a process associated with increased neutrophilia and that depended on γδT cells and IL-17A. Last, combined delivery of IL-7 and α-galactosylceramide (α-GalCer), a potent agonist for invariant NKT (iNKT) cells, conferred an almost total protection in terms of survival, an effect associated with enhanced IL-17 production by innate T cells and neutrophilia. Collectively, we provide a proof of concept that IL-7 enables fine-tuning of innate T- cell functions. This might pave the way for considering IL-7 as an innovative biotherapeutic against bacterial infection.

Published
2020

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