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1. PCSK9 inhibition protects mice from food allergy

Author

Lorant, Victoria, Klein, Martin, Garçon, Damien, Sotin, Thibaud, Frey, Samuel, Cheminant, Marie-Aude, Ayer, Audrey, Croyal, Mikaël, Flet, Laurent, Rimbert, Antoine, Colas, Luc, Cariou, Bertrand, Bouchaud, Grégory, and Le May, Cédric

Published
2024
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4. PCSK9 inhibition protects mice from food allergy

Author

Lorant, Victoria, primary, Klein, Martin, additional, Garcon, Damien, additional, Sotin, Thibaud, additional, Frey, Samuel, additional, Cheminant, Marie-Aude, additional, Ayer, Audrey, additional, Croyal, Mikaël, additional, Flet, Laurent, additional, Colas, Luc, additional, Cariou, Bertrand, additional, Bouchaud, Grégory, additional, and Le May, Cedric, additional

Published
2023
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5. Rac GTPase dependent cell signaling drives eosinophilic function in severe asthma.

Author

Hassoun, Dorian, primary, Bergereau, Hugo, additional, Rousselle, Morgane, additional, Cheminant, Marie-Aude, additional, Brosseau, Carole, additional, Jouand, Nicolas, additional, Sagan, Christine, additional, Bouchaud, Grégory, additional, Brouard, Sophie, additional, Blanc, François-Xavier, additional, Loirand, Gervaise, additional, Sauzeau, Vincent, additional, and BERGEREAU, Hugo, additional

Published
2023
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9. Supplementary Methods from The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer

Author

Badoual, Cécile, primary, Bouchaud, Grégory, primary, Agueznay, Nour El Houda, primary, Mortier, Erwan, primary, Hans, Stéphane, primary, Gey, Alain, primary, Fernani, Fahima, primary, Peyrard, Séverine, primary, -Puig, Pierre Laurent, primary, Bruneval, Patrick, primary, Sastre, Xavier, primary, Plet, Ariane, primary, Garrigue-Antar, Laure, primary, Quintin-Colonna, Françoise, primary, Fridman, Wolf H., primary, Brasnu, Daniel, primary, Jacques, Yannick, primary, and Tartour, Eric, primary

Published
2023
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10. Supplementary Figure 5 from The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer

Author

Badoual, Cécile, primary, Bouchaud, Grégory, primary, Agueznay, Nour El Houda, primary, Mortier, Erwan, primary, Hans, Stéphane, primary, Gey, Alain, primary, Fernani, Fahima, primary, Peyrard, Séverine, primary, -Puig, Pierre Laurent, primary, Bruneval, Patrick, primary, Sastre, Xavier, primary, Plet, Ariane, primary, Garrigue-Antar, Laure, primary, Quintin-Colonna, Françoise, primary, Fridman, Wolf H., primary, Brasnu, Daniel, primary, Jacques, Yannick, primary, and Tartour, Eric, primary

Published
2023
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11. Data from The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer

Author

Badoual, Cécile, primary, Bouchaud, Grégory, primary, Agueznay, Nour El Houda, primary, Mortier, Erwan, primary, Hans, Stéphane, primary, Gey, Alain, primary, Fernani, Fahima, primary, Peyrard, Séverine, primary, -Puig, Pierre Laurent, primary, Bruneval, Patrick, primary, Sastre, Xavier, primary, Plet, Ariane, primary, Garrigue-Antar, Laure, primary, Quintin-Colonna, Françoise, primary, Fridman, Wolf H., primary, Brasnu, Daniel, primary, Jacques, Yannick, primary, and Tartour, Eric, primary

Published
2023
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12. Supplementary Figure 3 from The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer

Author

Badoual, Cécile, primary, Bouchaud, Grégory, primary, Agueznay, Nour El Houda, primary, Mortier, Erwan, primary, Hans, Stéphane, primary, Gey, Alain, primary, Fernani, Fahima, primary, Peyrard, Séverine, primary, -Puig, Pierre Laurent, primary, Bruneval, Patrick, primary, Sastre, Xavier, primary, Plet, Ariane, primary, Garrigue-Antar, Laure, primary, Quintin-Colonna, Françoise, primary, Fridman, Wolf H., primary, Brasnu, Daniel, primary, Jacques, Yannick, primary, and Tartour, Eric, primary

Published
2023
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13. Supplementary Figure 4 from The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer

Author

Badoual, Cécile, primary, Bouchaud, Grégory, primary, Agueznay, Nour El Houda, primary, Mortier, Erwan, primary, Hans, Stéphane, primary, Gey, Alain, primary, Fernani, Fahima, primary, Peyrard, Séverine, primary, -Puig, Pierre Laurent, primary, Bruneval, Patrick, primary, Sastre, Xavier, primary, Plet, Ariane, primary, Garrigue-Antar, Laure, primary, Quintin-Colonna, Françoise, primary, Fridman, Wolf H., primary, Brasnu, Daniel, primary, Jacques, Yannick, primary, and Tartour, Eric, primary

Published
2023
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14. Supplementary Tables 1-4 from The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer

Author

Badoual, Cécile, primary, Bouchaud, Grégory, primary, Agueznay, Nour El Houda, primary, Mortier, Erwan, primary, Hans, Stéphane, primary, Gey, Alain, primary, Fernani, Fahima, primary, Peyrard, Séverine, primary, -Puig, Pierre Laurent, primary, Bruneval, Patrick, primary, Sastre, Xavier, primary, Plet, Ariane, primary, Garrigue-Antar, Laure, primary, Quintin-Colonna, Françoise, primary, Fridman, Wolf H., primary, Brasnu, Daniel, primary, Jacques, Yannick, primary, and Tartour, Eric, primary

Published
2023
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15. Supplementary Figure 1 from The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer

Author

Badoual, Cécile, primary, Bouchaud, Grégory, primary, Agueznay, Nour El Houda, primary, Mortier, Erwan, primary, Hans, Stéphane, primary, Gey, Alain, primary, Fernani, Fahima, primary, Peyrard, Séverine, primary, -Puig, Pierre Laurent, primary, Bruneval, Patrick, primary, Sastre, Xavier, primary, Plet, Ariane, primary, Garrigue-Antar, Laure, primary, Quintin-Colonna, Françoise, primary, Fridman, Wolf H., primary, Brasnu, Daniel, primary, Jacques, Yannick, primary, and Tartour, Eric, primary

Published
2023
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16. Supplementary Figure 2 from The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer

Author

Badoual, Cécile, primary, Bouchaud, Grégory, primary, Agueznay, Nour El Houda, primary, Mortier, Erwan, primary, Hans, Stéphane, primary, Gey, Alain, primary, Fernani, Fahima, primary, Peyrard, Séverine, primary, -Puig, Pierre Laurent, primary, Bruneval, Patrick, primary, Sastre, Xavier, primary, Plet, Ariane, primary, Garrigue-Antar, Laure, primary, Quintin-Colonna, Françoise, primary, Fridman, Wolf H., primary, Brasnu, Daniel, primary, Jacques, Yannick, primary, and Tartour, Eric, primary

Published
2023
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17. Supplementary Figure Legends 1-5 from The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer

Author

Badoual, Cécile, primary, Bouchaud, Grégory, primary, Agueznay, Nour El Houda, primary, Mortier, Erwan, primary, Hans, Stéphane, primary, Gey, Alain, primary, Fernani, Fahima, primary, Peyrard, Séverine, primary, -Puig, Pierre Laurent, primary, Bruneval, Patrick, primary, Sastre, Xavier, primary, Plet, Ariane, primary, Garrigue-Antar, Laure, primary, Quintin-Colonna, Françoise, primary, Fridman, Wolf H., primary, Brasnu, Daniel, primary, Jacques, Yannick, primary, and Tartour, Eric, primary

Published
2023
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18. Critical features of an in vitro intestinal absorption model to study the first key aspects underlying food allergen sensitization

Author

l’Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (France), Centro de Biotecnología y Genómica de Plantas (España), Universidad Politécnica de Madrid, CSIC-UAM - Instituto de Investigación en Ciencias de la Alimentación (CIAL), Fundação para a Ciência e a Tecnologia (Portugal), Fondation pour la Recherche Médicale, Ministerio de Economía, Industria y Competitividad (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), Région des Pays de la Loire, Ministerio de Ciencia, Innovación y Universidades (España), Comissão de Coordenação e Desenvolvimento Regional do Norte (Portugal), European Commission, Ministry of Agriculture, Nature and Food Quality (The Netherlands), Dijk, Wieneke [0000-0003-1676-7751], Villa, Caterina [0000-0002-9471-3612], Benedé, Sara [0000-0002-9288-9438], Vassilopoulou, Emilia [0000-0002-2665-5908], Mafra, Isabel [0000-0001-5311-8895], Garrido-Arandía, María [0000-0001-6114-5754], Martínez Blanco, Mónica [0000-0003-1153-7957], Bouchaud, Gregory [0000-0002-3794-7287], Hoppenbrouwers, Tamara [0000-0002-1764-9100], Bavaro, Simona Lucia [0000-0002-5820-8088], Giblin, Linda [0000-0002-9354-3121], Knipping, Karen [0000-0002-3700-9047], Costa, Joana [0000-0002-8229-2902], Bastiaan-Net, Shanna [0000-0001-8922-7305], Dijk, Wieneke, Villa, Caterina, Benedé, Sara, Vassilopoulou, Emilia, Mafra, Isabel, Garrido-Arandía, María, Martínez-Blanco, Mónica, Bouchaud, Grégory, Hoppenbrouwers, Tamara, Bavaro, Simona L., Giblin, Linda, Knipping, Karen, Castro Reigía, Ana María, Delgado, Susana, Costa, Joana, Bastiaan-Net, Shanna, l’Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (France), Centro de Biotecnología y Genómica de Plantas (España), Universidad Politécnica de Madrid, CSIC-UAM - Instituto de Investigación en Ciencias de la Alimentación (CIAL), Fundação para a Ciência e a Tecnologia (Portugal), Fondation pour la Recherche Médicale, Ministerio de Economía, Industria y Competitividad (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), Région des Pays de la Loire, Ministerio de Ciencia, Innovación y Universidades (España), Comissão de Coordenação e Desenvolvimento Regional do Norte (Portugal), European Commission, Ministry of Agriculture, Nature and Food Quality (The Netherlands), Dijk, Wieneke [0000-0003-1676-7751], Villa, Caterina [0000-0002-9471-3612], Benedé, Sara [0000-0002-9288-9438], Vassilopoulou, Emilia [0000-0002-2665-5908], Mafra, Isabel [0000-0001-5311-8895], Garrido-Arandía, María [0000-0001-6114-5754], Martínez Blanco, Mónica [0000-0003-1153-7957], Bouchaud, Gregory [0000-0002-3794-7287], Hoppenbrouwers, Tamara [0000-0002-1764-9100], Bavaro, Simona Lucia [0000-0002-5820-8088], Giblin, Linda [0000-0002-9354-3121], Knipping, Karen [0000-0002-3700-9047], Costa, Joana [0000-0002-8229-2902], Bastiaan-Net, Shanna [0000-0001-8922-7305], Dijk, Wieneke, Villa, Caterina, Benedé, Sara, Vassilopoulou, Emilia, Mafra, Isabel, Garrido-Arandía, María, Martínez-Blanco, Mónica, Bouchaud, Grégory, Hoppenbrouwers, Tamara, Bavaro, Simona L., Giblin, Linda, Knipping, Karen, Castro Reigía, Ana María, Delgado, Susana, Costa, Joana, and Bastiaan-Net, Shanna

Abstract

New types of protein sources will enter our diet in a near future, reinforcing the need for a straightforward in vitro (cell-based) screening model to test and predict the safety of these novel proteins, in particular their potential risk for de novo allergic sensitization. The Adverse Outcome Pathway (AOP) for allergen sensitization describes the current knowledge of key events underlying the complex cellular interactions that proceed allergic food sensitization. Currently, there is no consensus on the in vitro model to study the intestinal translocation of proteins as well as the epithelial activation, which comprise the first molecular initiation events (ME1-3) and the first key event of the AOP, respectively. As members of INFOGEST, we have highlighted several critical features that should be considered for any proposed in vitro model to study epithelial protein transport in the context of allergic sensitization. In addition, we defined which intestinal cell types are indispensable in a consensus model of the first steps of the AOP, and which cell types are optional or desired when there is the possibility to create a more complex cell model. A model of these first key aspects of the AOP can be used to study the gut epithelial translocation behavior of known hypo- and hyperallergens, juxtaposed to the transport behavior of novel proteins as a first screen for risk management of dietary proteins. Indeed, this disquisition forms a basis for the development of a future consensus model of the allergic sensitization cascade, comprising also the other key events (KE2-5).

Published
2023

19. Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma

Author

Dijoux, Eléonore, primary, Klein, Martin, additional, Misme-Aucouturier, Barbara, additional, Cheminant, Marie-Aude, additional, de Carvalho, Marion, additional, Collin, Louise, additional, Hassoun, Dorian, additional, Delage, Erwan, additional, Gourdel, Mathilde, additional, Loirand, Gervaise, additional, Sauzeau, Vincent, additional, Magnan, Antoine, additional, and Bouchaud, Grégory, additional

Published
2023
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23. Prebiotic Supplementation During Gestation Induces a Tolerogenic Environment and a Protective Microbiota in Offspring Mitigating Food Allergy

Author

Selle, Amandine, Brosseau, Carole, Dijk, Wieneke, Duval, Angéline, Bouchaud, Grégory, Rousseaux, Anais, Bruneau, Aurélia, Cherbuy, Claire, Mariadassou, Mahendra, Cariou, Véronique, Barbarot, Sebastien, and Bodinier, Marie

Subjects
Male, food allergy, immune tolerance, gut microbiota, Immunology, Inulin, Gastrointestinal Microbiome, Mice, Prebiotics, Pregnancy, Prenatal Exposure Delayed Effects, Dietary Supplements, Animals, Immunology and Allergy, Female, Food Hypersensitivity, Original Research
Abstract

Food allergy is associated with alterations in the gut microbiota, epithelial barrier, and immune tolerance. These dysfunctions are observed within the first months of life, indicating that early intervention is crucial for disease prevention. Preventive nutritional strategies with prebiotics are an attractive option, as prebiotics such as galacto-oligosaccharides and inulin can promote tolerance, epithelial barrier reinforcement, and gut microbiota modulation. Nonetheless, the ideal period for intervention remains unknown. Here, we investigated whether galacto-oligosaccharide/inulin supplementation during gestation could protect offspring from wheat allergy development in BALB/cJRj mice. We demonstrated that gestational prebiotic supplementation promoted the presence of beneficial strains in the fecal microbiota of dams during gestation and partially during mid-lactation. This specific microbiota was transferred to their offspring and maintained to adulthood. The presence of B and T regulatory immune cell subsets was also increased in the lymph nodes of offspring born from supplemented mothers, suggestive of a more tolerogenic immune environment. Indeed, antenatal prebiotic supplementation reduced the development of wheat allergy symptoms in offspring. Our study thus demonstrates that prebiotic supplementation during pregnancy induces, in the offspring, a tolerogenic environment and a microbial imprint that mitigates food allergy development.

Published
2022
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24. La colère comme enjeu d’un choix générique dans la lyrique antique

Author

Bouchaud, Grégory

Subjects
Lyrisme, Pindare, Horace, Colère, Archiloque
Abstract

Cet article observe, à partir des œuvres d’Archiloque et de Pindare puis des Odes d’Horace, si le genre dit « lyrique » peut se laisser cerner par l’acceptation ou le refus de la colère en tant que motif valable d’inspiration. La dialectique éloge/blâme sous-tend une grande partie de l’évolution de l’inspiration des poètes lyriques et la colère les divise en deux camps, l’un se réclamant d’une veine parénétique héritée d’Hésiode et l’autre d’une veine satirique provenant de la poésie iambique.

Published
2022
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25. Deamidation and Enzymatic Hydrolysis of Gliadins Alter Their Processing by Dendritic Cells in Vitro

Author

Villemin, Clélia, Tranquet, Olivier, Solé-Jamault, Véronique, Smit, Joost J, Pieters, Raymond H H, Denery-Papini, Sandra, Bouchaud, Grégory, One Health Toxicologie, dIRAS RA-1, One Health Toxicologie, dIRAS RA-1, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Utrecht University [Utrecht]

Subjects
0106 biological sciences, [SDV]Life Sciences [q-bio], Peptide, Wheat Hypersensitivity, 01 natural sciences, Gliadin, gliadins, Mice, Hydrolysis, Enzymatic hydrolysis, Animals, Humans, dendritic cells, Deamidation, Cells, Cultured, Triticum, chemistry.chemical_classification, Mice, Inbred C3H, biology, Chemistry, 010401 analytical chemistry, food and beverages, nutritional and metabolic diseases, T-Lymphocytes, Helper-Inducer, General Chemistry, allergy, digestive system diseases, In vitro, 0104 chemical sciences, deamidation, hydrolysis, Biochemistry, Biocatalysis, biology.protein, dendritic, cells, General Agricultural and Biological Sciences, Hydrophobic and Hydrophilic Interactions, deamination, CD80, Intracellular, 010606 plant biology & botany
Abstract

International audience; Gliadins are major wheat allergens. Their treatment by acid or enzymatic hydrolysis has been shown to modify their allergenic potential. As the interaction of food proteins with dendritic cells (DCs) is a key event in allergic sensitization, we wished to investigate whether deamidation and enzymatic hydrolysis influence gliadin processing by DC and to examine the capacity of gliadins to activate DCs. We compared the uptake and degradation of native and modified gliadins by DCs using mouse bone marrow-derived DCs. We also analyzed the effects of these interactions on the phenotypes of DCs and T helper (Th) lymphocytes. Modifying gliadins induced a change in physicochemical properties (molecular weight, hydrophobicity, and sequence) and also in the peptide size. These alterations in turn led to increased uptake and intracellular degradation of the proteins by DCs. Native gliadins (NGs) (100 μg/mL), but not modified gliadins, increased the frequency of DC expressing CD80 (15.41 ± 2.36% vs 6.81 ± 1.10%, p < 0.001), CCR7 (28.53 ± 8.17% vs 17.88 ± 2.53%, p < 0.001), CXCR4 (70.14 ± 4.63% vs 42.82 ± 1.96%, p < 0.001), and CCR7-dependent migration (2.46 ± 1.45 vs 1.00 ± 0.22, p < 0.01) compared with NGs. This was accompanied by Th lymphocyte activation (30.37 ± 3.87% vs 21.53 ± 3.14%, p < 0.1) and proliferation (16.39 ± 3.97% vs 9.31 ± 2.80%, p > 0.1). Moreover, hydrolysis decreases the peptide size and induces an increase in gliadin uptake and degradation. Deamidation and extensive enzymatic hydrolysis of gliadins modify their interaction with DCs, leading to alteration of their immunostimulatory capacity. These findings demonstrate the strong relationship between the biochemical characteristics of proteins and immune cell interactions.

Published
2019

27. Acid Hydrolysis of Gluten Enhances the Skin Sensitizing Potential and Drives Diversification of IgE Reactivity to Unmodified Gluten Proteins

Author

Ballegaard, Anne‐Sofie Ravn, primary, Castan, Laure, additional, Larsen, Jeppe Madura, additional, Piras, Cristian, additional, Villemin, Clélia, additional, Andersen, Daniel, additional, Madsen, Charlotte Bernhard, additional, Roncada, Paola, additional, Brix, Susanne, additional, Denery‐Papini, Sandra, additional, Mazzucchelli, Gabriel, additional, Bouchaud, Grégory, additional, and Bøgh, Katrine Lindholm, additional

Published
2021
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29. Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

Author

Lozano-Ojalvo, Daniel, Benedé, Sara, Antunes, Celia M., Bavaro, Simona L., Bouchaud, Grégory, Costa, Ana, Denery-Papini, Sandra, Díaz-Perales, Araceli, Garrido-Arandia, María, Gavrovic-Jankulovic, Marija, Hayen, Simone, Martínez-Blanco, Mónica, Molina, Elena, Monaci, Linda, Pieters, Raymond H.H., Villemin, Clelia, Wichers, Harry J., Wróblewska, Barbara, Willemsen, Linette E.M., Roggen, Erwin L., van Bilsen, Jolanda H.M., Afd Pharmacology, dIRAS RA-1, One Health Toxicologie, Pharmacology, Icahn School of Medicine at Mount Sinai, Partenaires INRAE, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Universidade de Évora, Institute of Sciences of Food Production (ISPA), Consiglio Nazionale delle Ricerche (CNR), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Centro de Biotecnologia y Genomica de Plantas - Centre for Plant Biotechnology and Genomics, University of Belgrade, Utrecht University [Utrecht], Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Wageningen University and Research Centre (WUR), PAN, 3Rs Managing and Consulting ApS, TNO, COST Action [FA1402], European Commission, Afd Pharmacology, dIRAS RA-1, One Health Toxicologie, and Pharmacology

Subjects
0301 basic medicine, Computer science, Iie-mediated food allergy, RAPID - Risk Analysis for Products in Development, Epithelial cells, Dendritic cells, sensitization, Allergic sensitization, 0302 clinical medicine, Life, Adverse Outcome Pathway, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Taverne, Allergies, Animal testing, Risk assessment, IgE-mediated food allergy, in vitro, In vitro models, Acquired immune system, 3. Good health, Health & Consumer Research, Biotechnology, Cells, Context (language use), Computational biology, 03 medical and health sciences, Adverse outcome pathway, T and B cells, Precursor frequency, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, AOP, Food, Health & Consumer Research, Nutrition, VLAG, B cells, food, Cellular pathways, Proteins, Adverse outcomes, In-vitro models, 030104 developmental biology, Immune system, 030228 respiratory system, Food, Food allergies, Cytology, Food sensitization, Food Science
Abstract

[Background] Before introducing proteins from new or alternative dietary sources into the market, a compressive risk assessment including food allergic sensitization should be carried out in order to ensure their safety. We have recently proposed the adverse outcome pathway (AOP) concept to structure the current mechanistic understanding of the molecular and cellular pathways evidenced to drive IgE-mediated food allergies. This AOP framework offers the biological context to collect and structure existing in vitro methods and to identify missing assays to evaluate sensitizing potential of food proteins. [Scope and approach] In this review, we provide a state-of-the-art overview of available in vitro approaches for assessing the sensitizing potential of food proteins, including their strengths and limitations. These approaches are structured by their potential to evaluate the molecular initiating and key events driving food sensitization. [Key findings and conclusions] The application of the AOP framework offers the opportunity to anchor existing testing methods to specific building blocks of the AOP for food sensitization. In general, in vitro methods evaluating mechanisms involved in the innate immune response are easier to address than assays addressing the adaptive immune response due to the low precursor frequency of allergen-specific T and B cells. Novel ex vivo culture strategies may have the potential to become useful tools for investigating the sensitizing potential of food proteins. When applied in the context of an integrated testing strategy, the described approaches may reduce, if not replace, current animal testing approaches., The authors are all part of the COST Action FA1402 entitled: Improving Allergy Risk Assessment Strategy for New Food Proteins (ImpARAS).

Published
2019

30. Separation of the Ca V 1.2‐Ca V 1.3 calcium channel duo prevents type 2 allergic airway inflammation

Author

Giang, Nicolas, primary, Mars, Marion, additional, Moreau, Marc, additional, Mejia, Jose E., additional, Bouchaud, Grégory, additional, Magnan, Antoine, additional, Michelet, Marine, additional, Ronsin, Brice, additional, Murphy, Geoffrey G., additional, Striessnig, Joerg, additional, Guéry, Jean‐Charles, additional, Pelletier, Lucette, additional, and Savignac, Magali, additional

Published
2021
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31. Essential role of smooth muscle Rac1 in severe asthma-associated airway remodelling

Author

Dilasser, Florian, Rose, Lindsay, Hassoun, Dorian, Klein, Martin, Rousselle, Morgane, Brosseau, Carole, Guignabert, Christophe, Taillé, Camille, Dombret, Marie, Di Candia, Leonarda, Heddebaut, Nicolas, Bouchaud, Grégory, Pretolani, Marina, Magnan, Antoine, Loirand, Gervaise, Sauzeau, Vincent, Sauzeau, Vincent, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, respiratory system, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, respiratory tract diseases
Abstract

International audience; Background Severe asthma is a chronic lung disease characterised by inflammation, airway hyperresponsiveness (AHR) and airway remodelling. The molecular mechanisms underlying uncontrolled airway smooth muscle cell (aSMC) proliferation involved in pulmonary remodelling are still largely unknown. Small G proteins of the Rho family (RhoA, Rac1 and Cdc42) are key regulators of smooth muscle functions and we recently demonstrated that Rac1 is activated in aSMC from allergic mice. The objective of this study was to assess the role of Rac1 in severe asthma-associated airway remodelling. Methods and results Immunofluorescence analysis in human bronchial biopsies revealed an increased Rac1 activity in aSMC from patients with severe asthma compared with control subjects. Inhibition of Rac1 by EHT1864 showed that Rac1 signalling controlled human aSMC proliferation induced by mitogenic stimuli through the signal transducer and activator of transcription 3 (STAT3) signalling pathway. In vivo, specific deletion of Rac1 in SMC or pharmacological inhibition of Rac1 by nebulisation of NSC23766 prevented AHR and aSMC hyperplasia in a mouse model of severe asthma. Moreover, the Rac1 inhibitor prevented goblet cell hyperplasia and epithelial cell hypertrophy whereas treatment with corticosteroids had less effect. Nebulisation of NSC23766 also decreased eosinophil accumulation in the bronchoalveolar lavage of asthmatic mice. Conclusion This study demonstrates that Rac1 is overactive in the airways of patients with severe asthma and is essential for aSMC proliferation. It also provides evidence that Rac1 is causally involved in AHR and airway remodelling. Rac1 may represent as an interesting target for treating both AHR and airway remodelling of patients with severe asthma.

Published
2021

32. Tonnerre de Brest ! Des Journées de Recherche Respiratoires 2020 pas comme les autres…

Author

UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service de pneumologie, Annesi-Maesano, Isabella, Bonniaud, Philippe, Bouchaud, Grégory, Boyer, Laurent, Frossard, Nelly, Gazzeri, Sylvie, Gosset, Philippe, Gras, Delphine, Guibert, Christelle, Guignabert, Christophe, Mari, Bernard, Matécki, Stéfan, Morélot, Capucine, Pilette, Charles, Planes, Carole, Plantier, Laurent, Polette, Myriam, Si-Tahar, Mustapha, Taillé, Camille, Vachier, Isbelle, membres du comité J2R, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service de pneumologie, Annesi-Maesano, Isabella, Bonniaud, Philippe, Bouchaud, Grégory, Boyer, Laurent, Frossard, Nelly, Gazzeri, Sylvie, Gosset, Philippe, Gras, Delphine, Guibert, Christelle, Guignabert, Christophe, Mari, Bernard, Matécki, Stéfan, Morélot, Capucine, Pilette, Charles, Planes, Carole, Plantier, Laurent, Polette, Myriam, Si-Tahar, Mustapha, Taillé, Camille, Vachier, Isbelle, and membres du comité J2R

Abstract

[Tonnerre de Brest! 2020 Respiratory Research Days like no others…].

Published
2021

33. Acid Hydrolysis of Gluten Enhances the Skin Sensitising Potential and Drives Diversification of IgE Reactivity to Unmodified Gluten Proteins

Author

Ballegaard, Anne-Sofie Ravn, Castan, Laure, Larsen, Jeppe Madura, Piras, Cristian, Villemin, Clélia, Andersen, Daniel, Madsen, Charlotte Bernhard, Roncada, Paola, Brix, Susanne, Denery-Papini, Sandra, Mazzucchelli, Gabriel, Bouchaud, Grégory, Bøgh, Katrine Lindholm, Ballegaard, Anne-Sofie Ravn, Castan, Laure, Larsen, Jeppe Madura, Piras, Cristian, Villemin, Clélia, Andersen, Daniel, Madsen, Charlotte Bernhard, Roncada, Paola, Brix, Susanne, Denery-Papini, Sandra, Mazzucchelli, Gabriel, Bouchaud, Grégory, and Bøgh, Katrine Lindholm

Abstract

Scope Personal care products containing hydrolysed gluten have been linked to spontaneous sensitisation through the skin, however the impact of the hydrolysate characteristics on the sensitising capacity is generally unknown. Methods and Results The physicochemical properties of five different wheat-derived gluten products (1 unmodified, 1 enzyme hydrolysed, and 3 acid hydrolysed) were investigated, and the skin sensitising capacity was determined in allergy-prone Brown Norway rats. Acid hydrolysed gluten products exhibited the strongest intrinsic sensitising capacity via the skin. All hydrolysed gluten products induced cross-reactivity to unmodified gluten in the absence of oral tolerance to wheat, but were unable to break tolerance in animals on a wheat-containing diet. Still, the degree of deamidation in acid hydrolysed products was associated with product-specific sensitisation in wheat tolerant rats. Sensitisation to acid hydrolysed gluten products was associated with a more diverse IgE reactivity profile to unmodified gluten proteins compared to sensitisation induced by unmodified gluten or enzyme hydrolysed gluten. Conclusion Acid hydrolysis enhances the skin sensitising capacity of gluten and drives IgE reactivity to more gluten proteins. This property of acid hydrolysed gluten may be related to the degree of product deamidation, and could be a strong trigger of wheat allergy in susceptible individuals.

Published
2021

34. Der p 2.1 Peptide Abrogates House Dust Mites-Induced Asthma Features in Mice and Humanized Mice by Inhibiting DC-Mediated T Cell Polarization

Author

Klein, Martin, Colas, Luc, Cheminant, Marie-Aude, Brosseau, Carole, Sauzeau, Vincent, Magnan, Antoine, Bouchaud, Grégory, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Nantes (UN), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), Fondation du Souffle, Fond de Dotation de Recherche en Santé Respiratoire, Région Pays de la Loire., ANR: ANR-16-IDEX-0007,national agency and future investment under the program ANR-16-IDEX-0007, Unité de recherche de l'institut du thorax (ITX-lab), ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016), DUPRE, Olivier, and NExT (I-SITE) - - NExT (I-SITE)2016 - ANR-16-IDEX-0007 - IDEX - VALID

Subjects
Adult, Male, Immunology, Mice, SCID, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Arthropod Proteins, Mice, Th2 Cells, Mice, Inbred NOD, Animals, Humans, Antigens, Dermatophagoides, Prospective Studies, dendritic cells, Original Research, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Mice, Inbred BALB C, Pyroglyphidae, Cell Polarity, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Middle Aged, asthma, allergy, peptide, respiratory tract diseases, Disease Models, Animal, Treatment Outcome, Desensitization, Immunologic, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Th17 Cells, Female, T lymphocyte (T-cell), [SDV.IB]Life Sciences [q-bio]/Bioengineering, immunotherapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Peptides
Abstract

International audience; Asthma is a chronic airway disease often due to sensitization to aeroallergens, especially house dust mite allergens (HDMs). The Dermatophagoides pteronyssinus group 2 (Der p 2), is one of the most representative HDM allergens and is recognized by more than 90% of HDM-allergic patients. In mouse models, all asthma-related features can be prevented by prophylactic administration of Dermatophagoides pteronyssinus 2-derived peptide (Der p 2.1). However, it is unknown whether it is able to treat well-established asthma in mice and humans. We aimed here to evaluate the efficacy of Der p 2.1 immunotherapy in a mouse, humanized mouse, and asthmatic patients. Asthma related-features were analyzed through airway hyperresponsiveness (AHR), allergen-specific IgE, and lung histology in mice and humanized mice. Immune profile was analyzed using lung and blood from mice and severe asthmatic patients respectively. T cell and dendritic cell (DC) polarization was evaluated using co-culture of bone marrow derived cells (BMDCs) and naive T cell from naive mice. Mice and humanized mice both have a reduced AHR, lung tissue alteration, and HDM-specific IgE under Der p 2.1 treatment. Concerning the immune profile, T helper 2 cells (Th2) and T helper 17 cells (Th17) were significantly reduced in both mice and humanized mice lung and in peripheral blood mononuclear cells (PBMCs) from severe asthmatic patients after Der p 2.1 incubation. The downregulation of T cell polarization seems to be linked to an increase of IL-10-secreting DC under Der p 2.1 treatment in both mice and severe asthmatic patients. This study shows that allergen-derived peptide immunotherapy abrogates asthma-related features in mice and humanized mice by reducing Th2 and Th17 cells polarization via IL-10-secreting DC. These results suggest that Der p 2.1 peptide immunotherapy could be a promising approach to treat both Th2 and Th17 immunity in asthma.

Published
2020

35. Deamidation and Enzymatic Hydrolysis of Gliadins Alter Their Processing by Dendritic Cells in Vitro

Author

One Health Toxicologie, dIRAS RA-1, Villemin, Clélia, Tranquet, Olivier, Solé-Jamault, Véronique, Smit, Joost J, Pieters, Raymond H H, Denery-Papini, Sandra, Bouchaud, Grégory, One Health Toxicologie, dIRAS RA-1, Villemin, Clélia, Tranquet, Olivier, Solé-Jamault, Véronique, Smit, Joost J, Pieters, Raymond H H, Denery-Papini, Sandra, and Bouchaud, Grégory

Published
2020

36. Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins?

Author

Castan, Laure, Bøgh, Katrine Lindholm, Maryniak, Natalia Zofia, Epstein, Michelle M, Kazemi, Sahar, O'Mahony, Liam, Bodinier, Marie, Smit, Joost J, van Bilsen, Jolanda H M, Blanchard, Carine, Głogowski, Robert, Kozáková, Hana, Schwarzer, Martin, Noti, Mario, de Wit, Nicole, Bouchaud, Grégory, Bastiaan-Net, Shanna, Castan, Laure, Bøgh, Katrine Lindholm, Maryniak, Natalia Zofia, Epstein, Michelle M, Kazemi, Sahar, O'Mahony, Liam, Bodinier, Marie, Smit, Joost J, van Bilsen, Jolanda H M, Blanchard, Carine, Głogowski, Robert, Kozáková, Hana, Schwarzer, Martin, Noti, Mario, de Wit, Nicole, Bouchaud, Grégory, and Bastiaan-Net, Shanna

Abstract

Significant efforts are necessary to introduce new dietary protein sources to feed a growing world population while maintaining food supply chain sustainability. Such a sustainable protein transition includes the use of highly modified proteins from side streams or the introduction of new protein sources that may lead to increased clinically relevant allergic sensitization. With food allergy being a major health problem of increasing concern, understanding the potential allergenicity of new or modified proteins is crucial to ensure public health protection. The best predictive risk assessment methods currently relied on are in vivo models, making the choice of endpoint parameters a key element in evaluating the sensitizing capacity of novel proteins. Here, we provide a comprehensive overview of the most frequently used in vivo and ex vivo endpoints in murine food allergy models, addressing their strengths and limitations for assessing sensitization risks. For optimal laboratory-to-laboratory reproducibility and reliable use of predictive tests for protein risk assessment, it is important that researchers maintain and apply the same relevant parameters and procedures. Thus, there is an urgent need for a consensus on key food allergy parameters to be applied in future food allergy research in synergy between both knowledge institutes and clinicians.

Published
2020

37. Engineering a safe monoclonal anti‐human IL‐2 that is effective in a murine model of food allergy and asthma.

Author

Klein, Martin, Misme‐Aucouturier, Barbara, Cheminant, Marie‐Aude, De Carvalho, Marion, Wauters, Marie, Tranquet, Olivier, Magnan, Antoine, and Bouchaud, Grégory

Subjects
FOOD allergy, REGULATORY T cells, INNATE lymphoid cells, RESPIRATORY allergy, ASTHMA, AIRWAY (Anatomy), WHEAT breeding
Abstract

Background: Regulatory T cells (Tregs) are known to protect against allergies. Moreover, the decrease in the frequency and efficiency of Tregs amplifies allergic symptoms. Aim: This study investigated whether expanding Tregs in vivo with an IL‐2/IL‐2 antibody complex could be safe, well tolerated and efficient in a therapeutic setting in allergies. Methods: We produced an anti‐IL‐2 antibody (1C6) and demonstrated that when it is complexed to human IL‐2, it increases IL‐2 efficiency to induce Tregs in vivo without any detectable side effects. Furthermore, the IL‐2/1C6 complex induces an increase in Helios expression by Tregs, suggesting that it not only elevated Treg numbers but also boosted their functions. Using mouse models of house‐dust‐mite‐induced airway inflammation and wheat‐gliadin‐induced food allergies, we investigated the therapeutic potential of the IL‐2/1C6 complex in allergies. Results: IL‐2/1C6 treatment significantly reduced allergic symptoms, specific IgE production, the adaptive immune response and tissue damage. Interestingly, IL‐2/1C6 treatment modulated innate lymphoid cells by increasing ILC2s in asthma and decreasing ILC3s in food allergies. Conclusion: In conclusion,complexed IL‐2/anti‐IL‐2 may restore Treg numbers and function in respiratory and food allergies, thereby improving allergic markers and symptoms. Our IL‐2/anti‐IL‐2 complex offers new hope for reestablishing immune tolerance in patients with allergies. [ABSTRACT FROM AUTHOR]

Published
2022
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38. Separation of the CaV1.2‐CaV1.3 calcium channel duo prevents type 2 allergic airway inflammation.

Author

Giang, Nicolas, Mars, Marion, Moreau, Marc, Mejia, Jose E., Bouchaud, Grégory, Magnan, Antoine, Michelet, Marine, Ronsin, Brice, Murphy, Geoffrey G., Striessnig, Joerg, Guéry, Jean‐Charles, Pelletier, Lucette, and Savignac, Magali

Subjects
CALCIUM channels, TH2 cells, T cells, INFLAMMATION, HOMEOSTASIS
Abstract

Background: Voltage‐gated calcium (Cav1) channels contribute to T‐lymphocyte activation. Cav1.2 and Cav1.3 channels are expressed in Th2 cells but their respective roles are unknown, which is investigated herein. Methods: We generated mice deleted for Cav1.2 in T cells or Cav1.3 and analyzed TCR‐driven signaling. In this line, we developed original fast calcium imaging to measure early elementary calcium events (ECE). We also tested the impact of Cav1.2 or Cav1.3 deletion in models of type 2 airway inflammation. Finally, we checked whether the expression of both Cav1.2 and Cav1.3 in T cells from asthmatic children correlates with Th2‐cytokine expression. Results: We demonstrated non‐redundant and synergistic functions of Cav1.2 and Cav1.3 in Th2 cells. Indeed, the deficiency of only one channel in Th2 cells triggers TCR‐driven hyporesponsiveness with weakened tyrosine phosphorylation profile, a strong decrease in initial ECE and subsequent reduction in the global calcium response. Moreover, Cav1.3 has a particular role in calcium homeostasis. In accordance with the singular roles of Cav1.2 and Cav1.3 in Th2 cells, deficiency in either one of these channels was sufficient to inhibit cardinal features of type 2 airway inflammation. Furthermore, Cav1.2 and Cav1.3 must be co‐expressed within the same CD4+ T cell to trigger allergic airway inflammation. Accordingly with the concerted roles of Cav1.2 and Cav1.3, the expression of both channels by activated CD4+ T cells from asthmatic children was associated with increased Th2‐cytokine transcription. Conclusions: Thus, Cav1.2 and Cav1.3 act as a duo, and targeting only one of these channels would be efficient in allergy treatment. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
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41. Exposure to endocrine disruptors and development of allergic diseases

Author

Guzylack-Piriou, Laurence, Bouchaud, Grégory, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), and Institut National de la Recherche Agronomique (INRA)

Subjects
endocrine disruptors, allergies, mouse model, immunity, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, childhood
Abstract

National audience; The prevalence of allergic diseases is increasing worldwide with unprecedented complexity and severity. The most common allergies in children are food allergies (8%), eczema (10%) and asthma (10%). The exact causes of this increase are not fully understood. Notably, human exposure to environmental pollutants such as endocrine disruptors (EDs) has attracted attention in recent years. This review highlights recent research exploring the effects of ED exposure in allergic diseases. Among these EDs, bisphenol A, phthalates, triclosan and paraben have demonstrated harmful effects in terms of the development of allergies. Epidemiological studies have shown that they may act either directly on the immune system leading to disturbance of tolerance or indirectly via modulation gut microbiota. In addition, sex hormones, which are also deregulated by ED exposure, promote allergic sensitization in animal models and may cause atopic disorders in humans. These emerging data on the development of allergy following dietary and respiratory exposure to such chemicals demonstrate the critical value of understanding their mechanisms and preventing the associated risks.

Published
2019

42. From the hypothesis of hygiene to microbiota

Author

Bouchaud, Grégory, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), and Institut National de la Recherche Agronomique (INRA)

Subjects
Allergy, Microbiota, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Hygiene, Gut, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, ComputingMilieux_MISCELLANEOUS, Model
Abstract

National audience

Published
2019

43. Prébiotiques

Author

Bodinier, Marie, Bouchaud, Grégory, Michel, Catherine, Champ, Martine, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Coxam V & Cardigny JM

Subjects
[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2019

44. CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

Author

Bousseau, Carole, Durand, Maxim, Colas, Luc, Durand, Eugenie, Foureau, Aurore, Cheminant, Marie-Aude, Bouchaud, Grégory, Castan, Laure, Klein, Martin, Magnan, Antoine, Brouard, Sophie, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), INRA Centre Angers-Nantes [Nantes, France], CIC biothérapies CBT 0503 [Nantes], Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), This work was supported by a grant from l’Institut de Recherche en Santé Respiratoire-Pays de la Loire. This work was achieved in the context of the BASAL project financed by Région Pays de la Loire and the IHU-Cesti project, the DHU Oncogreffe and the LabEX IGO thanks to French government financial support managed by the National Research Agency via the Investment into the Future program (ANR-10-IBHU-005 and ANR-11-LABX-0016-01). The IHU-Cesti project is also supported by Nantes Métropole and Région Pays de la Loire., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Unité de recherche de l'institut du thorax (ITX-lab), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), and Institut National de la Recherche Agronomique (INRA)

Subjects
Adult, Male, severe asthma, [SDV.IMM] Life Sciences [q-bio]/Immunology, MAP Kinase Signaling System, Immunology, Cell Communication, Mitochondrial Dynamics, Severity of Illness Index, Tetraspanin 29, Mice, effector T cells, T-Lymphocyte Subsets, regulatory B cells, CD9(+) B cells, apoptosis, Animals, Humans, Prospective Studies, Lung, Original Research, Aged, B-Lymphocytes, Regulatory, CD9+ B cells, Middle Aged, G1 Phase Cell Cycle Checkpoints, Asthma, Interleukin-10, Disease Models, Animal, embryonic structures, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, CD9 + B cells
Abstract

International audience; CD9 was recently identified as a marker of murine IL-10-competent regulatory B cells. Functional impairments or defects in CD9 + IL-10-secreting regulatory B cells are associated with enhanced asthma-like inflammation and airway hyperresponsiveness. In mouse models, all asthma-related features can be abrogated by CD9 + B cell adoptive transfer. We aimed herein to decipher the profiles, features, and molecular mechanisms of the regulatory properties of CD9 + B cells in human and mouse. The profile of CD9 + B cells was analyzed using blood from severe asthmatic patients and normal and asthmatic mice by flow cytometry. The regulatory effects of mouse CD9 + B cells on effector T cell death, cell cycle arrest, apoptosis, and mitochondrial depolarization were determined using yellow dye, propidium iodide, Annexin V, and JC-1 staining. MAPK phosphorylation was analyzed by western blotting. Patients with severe asthma and asthmatic mice both harbored less CD19 + CD9 + B cells, although these cells displayed no defect in their capacity to induce T cell apoptosis. Molecular mechanisms of regulation of CD9 + B cells characterized in mouse showed that they induced effector T cell cycle arrest in sub G0/G1, leading to apoptosis in an IL-10-dependent manner. This process occurred through MAPK phosphorylation and activation of both the intrinsic and extrinsic pathways. This study characterizes the molecular mechanisms underlying the regulation of CD9 + B cells to induce effector T cell apoptosis in mice and humans via IL-10 secretion. Defects in CD9 + B cells in blood from patients with severe asthma reveal new insights into the lack of regulation of inflammation in these patients.

Published
2018

45. Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

Author

Afd Pharmacology, dIRAS RA-1, One Health Toxicologie, Pharmacology, Lozano-Ojalvo, Daniel, Benedé, Sara, Antunes, Celia M., Bavaro, Simona L., Bouchaud, Grégory, Costa, Ana, Denery-Papini, Sandra, Díaz-Perales, Araceli, Garrido-Arandia, María, Gavrovic-Jankulovic, Marija, Hayen, Simone, Martínez-Blanco, Mónica, Molina, Elena, Monaci, Linda, Pieters, Raymond H.H., Villemin, Clelia, Wichers, Harry J., Wróblewska, Barbara, Willemsen, Linette E.M., Roggen, Erwin L., van Bilsen, Jolanda H.M., Afd Pharmacology, dIRAS RA-1, One Health Toxicologie, Pharmacology, Lozano-Ojalvo, Daniel, Benedé, Sara, Antunes, Celia M., Bavaro, Simona L., Bouchaud, Grégory, Costa, Ana, Denery-Papini, Sandra, Díaz-Perales, Araceli, Garrido-Arandia, María, Gavrovic-Jankulovic, Marija, Hayen, Simone, Martínez-Blanco, Mónica, Molina, Elena, Monaci, Linda, Pieters, Raymond H.H., Villemin, Clelia, Wichers, Harry J., Wróblewska, Barbara, Willemsen, Linette E.M., Roggen, Erwin L., and van Bilsen, Jolanda H.M.

Published
2019

46. Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

Author

European Commission, Lozano-Ojalvo, Daniel, Benedé, Sara, Antunes, Celia M., Bavaro, Simona L., Bouchaud, Grégory, Costa, Ana, Denery-Papini, Sandra, Díaz-Perales, Araceli, Garrido-Arandia, María, Gavrovic-Jankulovic, Marija, Hayen, Simone, Martínez-Blanco, Mónica, Molina, Elena, Monaci, Linda, Pieters, Raymond H. H., Villemin, Clelia, Wichers, Harry J., Wróblewska, Barbara, Willemsen, Linette E. M., Roggen, Erwin L., Bilsen, Jolanda H. M. van, European Commission, Lozano-Ojalvo, Daniel, Benedé, Sara, Antunes, Celia M., Bavaro, Simona L., Bouchaud, Grégory, Costa, Ana, Denery-Papini, Sandra, Díaz-Perales, Araceli, Garrido-Arandia, María, Gavrovic-Jankulovic, Marija, Hayen, Simone, Martínez-Blanco, Mónica, Molina, Elena, Monaci, Linda, Pieters, Raymond H. H., Villemin, Clelia, Wichers, Harry J., Wróblewska, Barbara, Willemsen, Linette E. M., Roggen, Erwin L., and Bilsen, Jolanda H. M. van

Abstract

[Background] Before introducing proteins from new or alternative dietary sources into the market, a compressive risk assessment including food allergic sensitization should be carried out in order to ensure their safety. We have recently proposed the adverse outcome pathway (AOP) concept to structure the current mechanistic understanding of the molecular and cellular pathways evidenced to drive IgE-mediated food allergies. This AOP framework offers the biological context to collect and structure existing in vitro methods and to identify missing assays to evaluate sensitizing potential of food proteins. [Scope and approach] In this review, we provide a state-of-the-art overview of available in vitro approaches for assessing the sensitizing potential of food proteins, including their strengths and limitations. These approaches are structured by their potential to evaluate the molecular initiating and key events driving food sensitization. [Key findings and conclusions] The application of the AOP framework offers the opportunity to anchor existing testing methods to specific building blocks of the AOP for food sensitization. In general, in vitro methods evaluating mechanisms involved in the innate immune response are easier to address than assays addressing the adaptive immune response due to the low precursor frequency of allergen-specific T and B cells. Novel ex vivo culture strategies may have the potential to become useful tools for investigating the sensitizing potential of food proteins. When applied in the context of an integrated testing strategy, the described approaches may reduce, if not replace, current animal testing approaches.

Published
2019

47. 'Avant-propos', in: Le suicide. Question individuelle ou sociétale ?, Actes du colloque de Clermont-Ferrand des 12 et 13 juin 2014, G. Bouchaud, C. Crépiat, G. Derbac, A. Gayte-Papon de Lameigné et A. Juliet (dir.), Centre Michel de l'Hospital, 2018, pp. 13-14

Author

Bouchaud, Grégory, Crépiat, Caroline, Derbac, Gheorghe, Gayte-Papon de Lameigné, Anaïs, Juliet, Alice, Centre de Recherches sur les Littératures et la Sociopoétique (CELIS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Michel de l'Hospital : laboratoire de recherche en sciences juridiques et politiques (CMH ), Centre Michel de l'Hospital CMH EA 4232, and Charles-André Dubreuil, Pr de droit public, CMH EA 4232

Subjects
[SHS.DROIT]Humanities and Social Sciences/Law, question sociétale, ComputingMilieux_MISCELLANEOUS, suicide, question individuelle
Abstract

National audience

Published
2018

48. Le suicide. Question individuelle ou sociétale ?, Actes du colloque de Clermont-Ferrand des 12 et 13 juin 2014, G. Bouchaud, C. Crépiat, G. Derbac, A. Gayte-Papon de Lameigné et A. Juliet (dir.), Centre Michel de l'Hospital, 2018, 416 p

Author

Bouchaud, Grégory, Crépiat, Caroline, Derbac, Gheorghe, Gayte-Papon de Lameigné, Anaïs, Juliet, Alice, Centre de Recherches sur les Littératures et la Sociopoétique (CELIS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Michel de l'Hospital : laboratoire de recherche en sciences juridiques et politiques (CMH ), Le Puy de la Recherche, Centre Michel de l'Hospital CMH EA 4232, CELIS CEntre de recherches sur les LIttératures et la Sociopoétique EA 1002, Caroline Crépiat, doctorante en littérature française, UBP, Anaïs Gayte, doctorante en droit privé, UdA, Alice Juliet, doctorante en droit privé, UdA, Camille Moisan, doctorante en droit public, UdA, Grégory Bouchaud, docteur en lettres classiques, UBP, Gheorghe Derbac, doctorant en littérature française, UBP, and Charles-André Dubreuil, Pr de droit public, CMH EA 4232

Subjects
Durkheim, oeuvres québécoises contemporaines, [SHS.LITT]Humanities and Social Sciences/Literature, responsabilité, attaques-suicides, nihilisme, droit pénal, [SHS.PSY]Humanities and Social Sciences/Psychology, George Sand, horreur, suicide du salarié, [SHS]Humanities and Social Sciences, [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, légalisation pénale, [SHS.DROIT]Humanities and Social Sciences/Law, révolte politique, autopsies psychosociales, représentation du suicide, homicides-suicides intrafamiliaux, faute inexcusable de l'employeur, martyr, ancienne Rome, [SHS.SOCIO]Humanities and Social Sciences/Sociology, mort volontaire, destin du collectif, métaphore, suicide par le feu, [SHS.PHIL]Humanities and Social Sciences/Philosophy, question sociétale, collectivité, tabou, psychopathologie, mécanismes du suicide, rire, assister au suicide, droit de l'homme, suicides en Auvergne de 2008 à 2010, coopération des tiers, Cesare Pavese, question individuelle, sociologie du suicide, attentats suicides, aspects médico-légaux, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, roman naturaliste, légitimation du suicide, médiations journalistiques, Brescia, Balleti Verdi, psychopathologie du suicide, suicide en détention, responsabilité civile de l'employeur, scandale, vulnérabilité, décision individuelle, suicide, islam radical, tentative de suicide, acte, normalité, Chat Noir, euthanasie, mort, individu, approche médicale au XIXe siècle en France, service public pénitentiaire, [SHS.SCIPO]Humanities and Social Sciences/Political science, Zola, non-altruisme, interdiction du suicide, société tchèque, suicide assisté, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Chateaubriand, ars moriendi, protester, morale, cinéma, [SHS.HIST]Humanities and Social Sciences/History, société, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, volonté
Abstract

National audience; Le suicide : question individuelle ou sociétale ? En juin 2014, lors de la première édition du Puy de la Recherche, un colloque s'est tenu à Clermont-Ferrand, dans le but de contribuer à l'analyse et à l'exploration de cette problématique. Il s'agissait de dégager les enjeux et les contradictions de ce tabou social, par un biais pluridisciplinaire : sciences humaines et sociales, droit, arts et médecine. Ce volume, qui en réunit les actes, donne une vision des débats sur la question qui animent actuellement la société, tout en proposant un retour sur ses perceptions et représentations passées. Il permettra ainsi au lecteur d'apprécier les différentes facettes de ce sujet, de ses diverses politiques de prévention et de sa condamnation morale à ses représentations les plus fantaisistes, en passant par sa réappropriation individuelle au nom d'idéaux divers.

Published
2018

49. A protocol for a trial assessing the efficacy of antenatal maternal supplementation with prebiotics on atopic dermatitis prevalence in children

Author

Barbarot, S., Aubert, H., Dochez, Vincent, Winer, Norbert, Bouchaud, Grégory, Bodinier, Marie, Centre hospitalier universitaire de Nantes (CHU Nantes), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
[SPI.GPROC] Engineering Sciences [physics]/Chemical and Process Engineering, [SDV.IDA]Life Sciences [q-bio]/Food engineering, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, [SDV.IDA] Life Sciences [q-bio]/Food engineering, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

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