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1. Flow cytometry analysis of endothelial cells and subsets of exhausted CD8+ T cells in murine tumor models

Author

Lucas Blanchard, Estefania Vina, Assia Asrir, Claire Tardiveau, Juliette Coudert, Robin Laffont, Dorian Tarroux, Sarah Bettini, Krystle Veerman, Fanny Lafouresse, Mélanie Pichery, Emilie Mirey, Elisabeth Bellard, Nathalie Ortega, and Jean-Philippe Girard

Subjects
Cell Biology, Cell isolation, Single Cell, Flow Cytometry/Mass Cytometry, Cancer, Health Sciences, Science (General), Q1-390
Abstract

Summary: Here, we present a protocol for flow cytometry analysis of endothelial cells (ECs) and CD8+ T cells in murine tumor models, at baseline and after cancer immunotherapy with anti-PD-1/anti-CTLA-4 antibodies. We provide gating strategies for identification of specific cell subsets including ECs from tumor-associated high endothelial venules (TA-HEVs), stem-like, and terminally exhausted CD8+ T cells. This protocol represents a valuable tool for the analysis of rare subsets of tumor ECs and CD8+ T cells with critical roles in antitumor immunity.For complete details on the use and execution of this protocol, please refer to Asrir et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Published
2022
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2. Food-grade TiO2 is trapped by intestinal mucus in vitro but does not impair mucin O-glycosylation and short-chain fatty acid synthesis in vivo: implications for gut barrier protection

Author

Pauline Talbot, Joanna M. Radziwill-Bienkowska, Jasper B. J. Kamphuis, Karine Steenkeste, Sarah Bettini, Véronique Robert, Marie-Louise Noordine, Camille Mayeur, Eric Gaultier, Philippe Langella, Catherine Robbe-Masselot, Eric Houdeau, Muriel Thomas, and Muriel Mercier-Bonin

Subjects
Food-grade TiO2, Gut barrier, Mucin O-glycans, Mucus, Short-chain fatty acids, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5
Abstract

Abstract Background Titanium dioxide (TiO2) particles are commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, the risk of gut barrier disruption is an increasing concern because of the presence of a nano-sized fraction. Food-grade E171 may interact with mucus, a gut barrier protagonist still poorly explored in food nanotoxicology. To test this hypothesis, a comprehensive approach was performed to evaluate in vitro and in vivo interactions between TiO2 and intestinal mucus, by comparing food-grade E171 with NM-105 (Aeroxyde P25) OECD reference nanomaterial. Results We tested E171-trapping properties of mucus in vitro using HT29-MTX intestinal epithelial cells. Time-lapse confocal laser scanning microscopy was performed without labeling to avoid modification of the particle surface. Near-UV irradiation of E171 TiO2 particles at 364 nm resulted in fluorescence emission in the visible range, with a maximum at 510 nm. The penetration of E171 TiO2 into the mucoid area of HT29-MTX cells was visualized in situ. One hour after exposure, TiO2 particles accumulated inside “patchy” regions 20 µm above the substratum. The structure of mucus produced by HT29-MTX cells was characterized by MUC5AC immunofluorescence staining. The mucus layer was thin and organized into regular “islands” located approximately 20 µm above the substratum. The region-specific trapping of food-grade TiO2 particles was attributed to this mucus patchy structure. We compared TiO2-mediated effects in vivo in rats after acute or sub-chronic oral daily administration of food-grade E171 and NM-105 at relevant exposure levels for humans. Cecal short-chain fatty acid profiles and gut mucin O-glycosylation patterns remained unchanged, irrespective of treatment. Conclusions Food-grade TiO2 is trapped by intestinal mucus in vitro but does not affect mucin O-glycosylation and short-chain fatty acid synthesis in vivo, suggesting the absence of a mucus barrier impairment under “healthy gut” conditions.

Published
2018
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3. Food-grade TiO2 is trapped by intestinal mucus in vitro but does not impair mucin O-glycosylation and short-chain fatty acid synthesis in vivo:implications for gut barrier protection

Author

Pauline Talbot, Joanna M. Radziwill-Bienkowska, Jasper B. J. Kamphuis, Karine Steenkeste, Sarah Bettini, Véronique Robert, Marie-Louise Noordine, Camille Mayeur, Eric Gaultier, Philippe Langella, Catherine Robbe-Masselot, Eric Houdeau, Muriel Thomas, Muriel Mercier-Bonin, CNRS, Université de Lille, MICrobiologie de l'ALImentation au Service de la Santé [MICALIS], Polska Akademia Nauk = Polish Academy of Sciences [PAN], ToxAlim [ToxAlim], Institut des Sciences Moléculaires d'Orsay [ISMO], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institute of Biochemistry and Biophysics, Pawinskiego 5a, 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), Institut des Sciences Moléculaires d’Orsay (ISMO), Centre National de la Recherche Scientifique (CNRS), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), and This work was funded by INRA in the frame of the 'Nutrition, Chemical Food Safety, and Consumer Behaviour' division (AlimH priority program 2013)

Subjects
Short-chain fatty acids, Mucus, lcsh:Medical technology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, lcsh:R855-855.5, lcsh:Biotechnology, lcsh:TP248.13-248.65, Gut barrier, Food-grade TiO2, Mucin O-glycans
Abstract

Background Titanium dioxide (TiO2) particles are commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, the risk of gut barrier disruption is an increasing concern because of the presence of a nano-sized fraction. Food-grade E171 may interact with mucus, a gut barrier protagonist still poorly explored in food nanotoxicology. To test this hypothesis, a comprehensive approach was performed to evaluate in vitro and in vivo interactions between TiO2 and intestinal mucus, by comparing food-grade E171 with NM-105 (Aeroxyde P25) OECD reference nanomaterial. Results We tested E171-trapping properties of mucus in vitro using HT29-MTX intestinal epithelial cells. Time-lapse confocal laser scanning microscopy was performed without labeling to avoid modification of the particle surface. Near-UV irradiation of E171 TiO2 particles at 364 nm resulted in fluorescence emission in the visible range, with a maximum at 510 nm. The penetration of E171 TiO2 into the mucoid area of HT29-MTX cells was visualized in situ. One hour after exposure, TiO2 particles accumulated inside “patchy” regions 20 µm above the substratum. The structure of mucus produced by HT29-MTX cells was characterized by MUC5AC immunofluorescence staining. The mucus layer was thin and organized into regular “islands” located approximately 20 µm above the substratum. The region-specific trapping of food-grade TiO2 particles was attributed to this mucus patchy structure. We compared TiO2-mediated effects in vivo in rats after acute or sub-chronic oral daily administration of food-grade E171 and NM-105 at relevant exposure levels for humans. Cecal short-chain fatty acid profiles and gut mucin O-glycosylation patterns remained unchanged, irrespective of treatment. Conclusions Food-grade TiO2 is trapped by intestinal mucus in vitro but does not affect mucin O-glycosylation and short-chain fatty acid synthesis in vivo, suggesting the absence of a mucus barrier impairment under “healthy gut” conditions.

Published
2018
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4. Food-grade TiO

Author

Pauline, Talbot, Joanna M, Radziwill-Bienkowska, Jasper B J, Kamphuis, Karine, Steenkeste, Sarah, Bettini, Véronique, Robert, Marie-Louise, Noordine, Camille, Mayeur, Eric, Gaultier, Philippe, Langella, Catherine, Robbe-Masselot, Eric, Houdeau, Muriel, Thomas, and Muriel, Mercier-Bonin

Subjects
Male, Titanium, Glycosylation, Surface Properties, Research, Mucins, Food-grade TiO2, Fatty Acids, Volatile, Mucin O-glycans, Mucus, Short-chain fatty acids, Intestinal Absorption, Gut barrier, Animals, Humans, Nanoparticles, Food Additives, Tissue Distribution, Intestinal Mucosa, Particle Size, Rats, Wistar, Cecum, HT29 Cells
Abstract

Background Titanium dioxide (TiO2) particles are commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, the risk of gut barrier disruption is an increasing concern because of the presence of a nano-sized fraction. Food-grade E171 may interact with mucus, a gut barrier protagonist still poorly explored in food nanotoxicology. To test this hypothesis, a comprehensive approach was performed to evaluate in vitro and in vivo interactions between TiO2 and intestinal mucus, by comparing food-grade E171 with NM-105 (Aeroxyde P25) OECD reference nanomaterial. Results We tested E171-trapping properties of mucus in vitro using HT29-MTX intestinal epithelial cells. Time-lapse confocal laser scanning microscopy was performed without labeling to avoid modification of the particle surface. Near-UV irradiation of E171 TiO2 particles at 364 nm resulted in fluorescence emission in the visible range, with a maximum at 510 nm. The penetration of E171 TiO2 into the mucoid area of HT29-MTX cells was visualized in situ. One hour after exposure, TiO2 particles accumulated inside “patchy” regions 20 µm above the substratum. The structure of mucus produced by HT29-MTX cells was characterized by MUC5AC immunofluorescence staining. The mucus layer was thin and organized into regular “islands” located approximately 20 µm above the substratum. The region-specific trapping of food-grade TiO2 particles was attributed to this mucus patchy structure. We compared TiO2-mediated effects in vivo in rats after acute or sub-chronic oral daily administration of food-grade E171 and NM-105 at relevant exposure levels for humans. Cecal short-chain fatty acid profiles and gut mucin O-glycosylation patterns remained unchanged, irrespective of treatment. Conclusions Food-grade TiO2 is trapped by intestinal mucus in vitro but does not affect mucin O-glycosylation and short-chain fatty acid synthesis in vivo, suggesting the absence of a mucus barrier impairment under “healthy gut” conditions. Electronic supplementary material The online version of this article (10.1186/s12951-018-0379-5) contains supplementary material, which is available to authorized users.

Published
2018

5. The site of tumor development determines immunogenicity via temporal mobilization of antigen-laden dendritic cells in draining lymph nodes

Author

Martine Guiraud, Nathalie T. Joncker, Sylvie Guerder, Sarah Bettini, and Delphine Boulet

Subjects
CD4-Positive T-Lymphocytes, 0301 basic medicine, Immunology, Antigen presentation, Priming (immunology), CD8-Positive T-Lymphocytes, Biology, Lymphocyte Activation, Mice, 03 medical and health sciences, Subcutaneous Tissue, Immune system, Antigen, Antigens, Neoplasm, Neoplasms, Animals, Immunology and Allergy, Cytotoxic T cell, Antigen Presentation, Follicular dendritic cells, Immunogenicity, Dendritic Cells, Dermis, Tumor antigen, 030104 developmental biology, Langerhans Cells, Lymph Nodes
Abstract

The elimination of solid tumors largely depends on effective T-cell priming by dendritic cells (DCs). For decades, studies focusing on antitumoral immune responses have been performed with tumors transplanted subcutaneously (s.c.). These studies however do not take into account the heterogeneous tissue distribution and functionality of the different DC subsets. Given the crucial role of DCs in inducing protective immune response, we postulated that the anatomic location of tumor development may greatly impact tumor immunogenicity. We therefore implanted tumor cells either in the DC-rich dermis environment or in the s.c. tissue that mainly contains macrophages and monocytes. We showed that intradermal (i.d.), but not s.c. tumors are rapidly rejected in a T-cell-dependent manner and induce protective T-cell responses. The rejection of i.d. tumors correlates with rapid recruitment of dermal DCs presenting the tumor antigen to both CD4 and CD8 T cells in the draining lymph nodes (dLNs). The same DC subsets were mobilized upon s.c. tumor transplantation but with delayed kinetics. Altogether, our results show that the anatomical site of tumor development influences tumor immunogenicity, notably by controlling the kinetics of DC mobilization in the draining LNs.

Published
2015
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6. Food-grade TIO2 pigment initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon

Author

Pierre, Fabrice H. F., Sarah Bettini, Jacques Dupuy, Nathalie Naud, Christel Cartier, Christine Coméra, Eric Gaultier, Jean Pierre Cravedi, Elisa Boutet-Robinet, Laurence Guzylack-Piriou, Eric Houdeau, 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), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), and Contaminants & Stress Cellulaire (ToxAlim-COMICS)

Subjects
[SDV]Life Sciences [q-bio], digestive, oral, and skin physiology, digestive system diseases
Abstract

Food-grade TIO2 pigment initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon. Digestive Disease Week (DDW)

Published
2017

7. Exposition orale aux nanoparticules de dioxyde de titane (TiO2) : du franchissement de l’épithélium buccal et intestinal au devenir et aux effets dans l’organisme

Author

Eric Houdeau, Sarah Bettini, 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), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Houdeau, Eric

Subjects
food.ingredient, système immunitaire, [SDV]Life Sciences [q-bio], Nanoparticle, Gastrointestinal mucosa, 010501 environmental sciences, white food pigment E171, 01 natural sciences, nanoparticules, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, food, In vivo, Food science, Daily exposure, Organism, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, additif alimentaire E171, Food additive, muqueuses buccales, barrière intestinale, In vitro, 3. Good health, intestinal barrier, immune system, chemistry, Titanium dioxide, nanoparticles, buccal mucosa
Abstract

Face à l’utilisation exponentielle des nanomatériaux dans des produits de consommation courante, dont l’alimentation, les conséquences pour l’homme d’une exposition quotidienne aux faibles doses de nanoparticules posent des questions de santé publique. Parmi les différentes voies d’exposition, la voie orale reste la moins documentée, alors que des nanomatériaux sont couramment utilisés comme additifs alimentaires, ou incorporés `a des emballages au contact des aliments, de l’eau, pour b´en´eficier de leurs propriétés texturantes, anti-microbiennes ou encore comme simples colorants. Les muqueuses buccales et gastro-intestinales sont les premières régions en contact avec les nanoparticules ingérées. Les nanoparticules franchissent ces barrières biologiques pour ensuite se distribuer au compartiment systémique. Bien que des différences existent entre catégories de nanoparticules, compte tenu de leurs propriétés physico-chimiques propres, de la dimension des particules primaires et de leur solubilité éventuelle, l’exemple pris dans cette revue avec le dioxyde de titane (TiO2) se veut démonstratif des études de toxicité orale menées in vivo et in vitro pour participer `à l’´évaluation du risque pour l’homme., As we are faced with the exponential use of nanomaterials in consumer products, including food, the consequences of daily exposure to nanoparticles at low doses set public health issues for humans. Among the different routes of exposure, the oral route remains the less documented, although nanomaterials are commonly used as food additives, or incorporated into packaging in contact with food or water, to provide their texturing and anti-microbial properties, or as simple colorant agents. The oral and gastrointestinal mucosa are the first regions in contact with the ingested nanoparticles. The latter cross these biological barriers, and distribute to the systemic compartment. Although differences exist between categories of nanoparticles, given differences in their physico-chemical properties, primary particle size and solubility, the example given in this review with titanium dioxide (TiO2) is intended to illustrate oral toxicity studies conducted in vivo and in vitro in order to contribute to the risk assessment in humans.

Published
2014
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8. Food-grade TiO 2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon

Author

Jean-Nicolas Audinot, Christel Cartier, Eric Gaultier, Fabrice Pierre, Eric Houdeau, Nathalie Naud, Marie Carrière, Matthieu Réfrégiers, Nathalie Thieriet, Sarah Bettini, Laurence Guzylack-Piriou, Dominique Thiaudière, Elisa Boutet-Robinet, Patrick Grysan, J. Dupuy, Solenn Reguer, Jean Pierre Cravedi, Sylviane Taché, Christine Coméra, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Materials Research and Technology (MRT) Department, Luxembourg Institute of Science and Technology (LIST), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), ANSES : PNR- EST-2013-024, NanoGut project, INRA, Contaminants & Stress Cellulaire (ToxAlim-COMICS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
0301 basic medicine, medicine.medical_specialty, Colorectal cancer, Crypt, Stimulation, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Biology, medicine.disease_cause, 03 medical and health sciences, Immune system, Internal medicine, medicine, risk factors, Multidisciplinary, technology, industry, and agriculture, Gastroenterology, Dendritic cell, 021001 nanoscience & nanotechnology, medicine.disease, 3. Good health, 030104 developmental biology, Endocrinology, 0210 nano-technology, Carcinogenesis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Homeostasis, Aberrant crypt foci
Abstract

Food-grade titanium dioxide (TiO2) containing a nanoscale particle fraction (TiO2-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO2-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer’s patches (PP) as observed with the TiO2-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO2-treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources.

Published
2017
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9. Food-grade TiO

Author

Sarah, Bettini, Elisa, Boutet-Robinet, Christel, Cartier, Christine, Coméra, Eric, Gaultier, Jacques, Dupuy, Nathalie, Naud, Sylviane, Taché, Patrick, Grysan, Solenn, Reguer, Nathalie, Thieriet, Matthieu, Réfrégiers, Dominique, Thiaudière, Jean-Pierre, Cravedi, Marie, Carrière, Jean-Nicolas, Audinot, Fabrice H, Pierre, Laurence, Guzylack-Piriou, and Eric, Houdeau

Subjects
Inflammation, Male, Titanium, Carcinogenesis, Colon, T-Lymphocytes, Administration, Oral, Cell Count, Epithelial Cells, Cell Separation, Dendritic Cells, Permeability, Article, Peyer's Patches, Liver, Food, Immune System, Animals, Cytokines, Homeostasis, Tissue Distribution, Rats, Wistar, Precancerous Conditions, DNA Damage, Subcellular Fractions
Abstract

Food-grade titanium dioxide (TiO2) containing a nanoscale particle fraction (TiO2-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO2-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer’s patches (PP) as observed with the TiO2-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO2-treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources.

Published
2016

10. Food-Grade TIO 2 Pigment Initiates Preneoplastic Lesions and Promotes Aberrant Crypt Development in the Rat Colon

Author

Nathalie Naud, Fabrice Pierre, Laurence Guzylack-Piriou, J. Dupuy, Jean-Pierre Cravedi, Christel Cartier, Christine Coméra, Sylviane Taché, Elisa Boutet, Eric Gaultier, Eric Houdeau, and Sarah Bettini

Subjects
010302 applied physics, medicine.medical_specialty, Pathology, Hepatology, digestive, oral, and skin physiology, Crypt, Gastroenterology, Food grade, 02 engineering and technology, Biology, 021001 nanoscience & nanotechnology, 01 natural sciences, digestive system diseases, Pigment, visual_art, Internal medicine, 0103 physical sciences, medicine, visual_art.visual_art_medium, 0210 nano-technology
Abstract

Food-grade TIO2 pigment initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon. Digestive Disease Week (DDW)

Published
2017
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11. Distribution dans l’intestin et impacts sur le système immunitaire de nanoparticules de dioxyde de titane (TiO2) après exposition orale chez le rat

Author

Sarah Bettini, Laurence Guzylack-Piriou, Eric Gaultier, Christel Cartier, Christine Coméra, Dominique Thiaudière, Mathieu Réfrégiers, Marie Carrière, Elisa Boutet-Robinet, Pierre, Fabrice H. F., Eric Houdeau, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), European Synchrotron Radiation Facility (ESRF), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), 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), 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

Catalog

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