Descriptor: "MESH: Natural Killer T-Cells" - Searchworks@Jio Institute Digital Library Search Results

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20 results on '"MESH: Natural Killer T-Cells"'

1. SLAM-associated protein favors the development of iNKT2 over iNKT17 cells

Author: Maria Leite-de-Moraes, Sylvain Latour, Gérard Eberl, Séverine Diem, Rachel Rignault-Bricard, Benoit Pasquier, Agnès Lehuen, André Veillette, Marie Laure Michel, Shinichiro Sawa, Bérangère Massot, Christelle Lenoir, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Coordination des Cellules et Morphogenèse / Heart Morphogenesis (Imagine - Institut Pasteur U1163), Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratory of Molecular Oncology, Clinical Research Institute of Montréal, This work was supported by grants from INSERM (Institut National de la Santé et de la Recherche Médicale), CNRS (Centre National de la Recherche Scientifique), ANR (Agence Nationale de la Recherche, ANR‐08‐MIEN‐012‐01, ANR‐2010‐MIDI‐005, and ANR‐10‐IAHU‐01), the Fondation ARC pour la Recherche sur le Cancer (France), the European Research Council (ERC‐2009‐AdG_20090506 n°FP7‐249816), and the Rare Diseases Fondation (France)., ANR-08-MIEN-0012,GENEBV,Susceptibilité génétique à l'infection par l'EBV et lymphocytes NKT(2008), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), European Project: 249816,EC:FP7:ERC,ERC-2009-AdG,PIDIMMUN(2010), Université Paris Descartes - Paris 5 (UPD5)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, MESH: Nuclear Receptor Subfamily 1, Group F, Member 3, Cellular differentiation, medicine.medical_treatment, MESH: Interleukin-17, [SDV]Life Sciences [q-bio], PLZF, Retinoic acid, MESH: T-Lymphocyte Subsets, Thymic development, MESH: Mice, Knockout, chemistry.chemical_compound, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Immunology and Allergy, MESH: Animals, Signaling Lymphocytic Activation Molecule Associated Protein, Cells, Cultured, Orphan receptor, Mice, Knockout, Interleukin-17, Cell Differentiation, Nuclear Receptor Subfamily 1, Group F, Member 3, Natural killer T cell, Cell biology, IL-17, Cytokine, Phenotype, SAP, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH: Immunophenotyping, MESH: Mice, Transgenic, Immunology, Mice, Transgenic, MESH: Signaling Lymphocytic Activation Molecule Associated Protein, Cell fate determination, Biology, MESH: Phenotype, Immunophenotyping, 03 medical and health sciences, medicine, Animals, Transcription factor, MESH: Mice, Interleukin 4, iNKT cells, IL-4, MESH: Interleukin-4, 030104 developmental biology, chemistry, MESH: Natural Killer T-Cells, MESH: Biomarkers, Natural Killer T-Cells, Interleukin-4, Biomarkers, 030215 immunology
Abstract: International audience; Invariant NKT (iNKT) cells differentiate in the thymus into three distinct lineages defined by their cytokine and transcription factor expression. Signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) is essential for early stages of iNKT cell development, but its role during terminal differentiation of iNKT1, iNKT2, or iNKT17 cells remains unclear. Taking advantage of SAP-deficient mice expressing a Vα14-Jα18 TCRα transgene, we found that SAP is critical not only for IL-4 production but also for the terminal differentiation of IL-4-producing iNKT2 cells. Furthermore, without SAP, the IL-17 producing subset is expanded, while IFN-γ-producing iNKT1 differentiation is only moderately compromised. Lack of SAP reduced the expression of the transcription factors GATA-3 and promyelocytic leukemia zinc finger, but enhanced the levels of retinoic acid receptor-related orphan receptor γt. In the absence of SAP, lineage commitment was actually shifted toward the emergence of iNKT17 over iNKT2 cells. Collectively, our data unveil a new critical regulatory function for SAP in thymic iNKT cell fate decisions.
Published: 2016

2. Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation

Author: Lionel Le Bourhis, Olivier Lantz, Yue Cui, Katarzyna Franciszkiewicz, Yvonne K. Mburu, Sylvie Rabot, Alexandra Kachaner, Emmanuel Martin, Claire Soudais, Stanislas Mondot, Virginie Premel, Livine Duban, Jean Jaubert, Molly A. Ingersoll, Jean-Pierre de Villartay, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biopathologie, Institut Curie [Paris], This work was supported by grants from INSERM, Agence Nationale de la Recherche (ANR), DIM Ile de France, Association pour la Recherche sur la Sclérose En Plaques (ARSEP), Institut Mérieux, and Institut Curie. Y.K. Mburu is a recipient of the Lloyd J. Old Memorial Award and is supported by an Irvington Institute postdoctoral fellowship from the Cancer Research Institute., Vougny, Marie-Christine, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Curie
Subjects: MESH: Minor Histocompatibility Antigens, MESH: Nuclear Receptor Subfamily 1, Group F, Member 3, Receptors, Antigen, T-Cell, alpha-beta, MESH: Chemotaxis, Leukocyte, MESH: Urinary Tract Infections, Lymphocyte Activation, MESH: Mice, Knockout, MESH: Histocompatibility Antigens Class I, MESH: Promyelocytic Leukemia Zinc Finger Protein, Mice, 0302 clinical medicine, Promyelocytic Leukemia Zinc Finger Protein, MESH: Animals, Mice, Knockout, 0303 health sciences, education.field_of_study, Lymphokines, MESH: Receptors, Antigen, T-Cell, alpha-beta, Microbiota, MESH: Polymorphism, Single Nucleotide, General Medicine, Nuclear Receptor Subfamily 1, Group F, Member 3, Natural killer T cell, MESH: Crosses, Genetic, Chemotaxis, Leukocyte, medicine.anatomical_structure, Phenotype, Radiation Chimera, Urinary Tract Infections, MESH: Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Kruppel-Like Transcription Factors, Research Article, MESH: Lymphocyte Count, [SDV.IMM] Life Sciences [q-bio]/Immunology, Lymphoid Tissue, MESH: Radiation Chimera, MESH: Mice, Transgenic, T cell, Population, Congenic, Kruppel-Like Transcription Factors, Mice, Transgenic, Mucosal associated invariant T cell, Biology, MESH: Phenotype, Polymorphism, Single Nucleotide, Minor Histocompatibility Antigens, 03 medical and health sciences, Mice, Congenic, MESH: Mice, Congenic, MESH: Mice, Inbred C57BL, MESH: Germ-Free Life, medicine, Animals, Germ-Free Life, Humans, MESH: Microbiota, Lymphocyte Count, Receptors, Cytokine, education, MESH: Lymphocyte Activation, MESH: Mice, Crosses, Genetic, 030304 developmental biology, MESH: Humans, MESH: Lymphokines, T-cell receptor, Histocompatibility Antigens Class I, Laboratory mouse, Gene rearrangement, Molecular biology, MESH: Receptors, Cytokine, Mice, Inbred C57BL, Disease Models, Animal, MESH: Natural Killer T-Cells, MESH: Lymphoid Tissue, Natural Killer T-Cells, MESH: Disease Models, Animal, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, Immunologic Memory, MESH: Female, 030215 immunology
Abstract: Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%-10% in blood). Despite strong evolutionary conservation of the invariant TCR-alpha chain and restricting molecule MR1, this population is rare in laboratory mouse strains (approximate to 0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-alpha locus and led to higher usage of the distal V alpha segments, including V alpha 19. We generated a MAIT(hl) congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44(+)) CD4(-)CD8(lo/neg) T cells with tissue-homing properties (CCR6*CCR7(-)). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18R alpha, and IL-12R beta and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptory gamma (R0R gamma t). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIT(hi) congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.
Published: 2015

3. Fine tuning by human CD1e of lipid-specific immune responses

Author: Gennaro De Libero, Lena Angman, Luigi Panza, Catherine Angénieux, Giulia Casorati, Steven A. Porcelli, Marco Cavallari, Paolo Dellabona, François Signorino-Gelo, Chengfeng Xia, Jacques Prandi, Luis F. Garcia-Alles, Germain Puzo, Martine Gilleron, Federica Facciotti, Peng George Wang, Lucia Mori, Facciotti, F, Cavallari, M, Angenieux, C, Garcia-Alles, L, Signorino-Gelo, F, Angman, L, Gilleron, M, Prandi, J, Puzo, G, Panza, L, Xia, C, Wang, P, Dellabona, P, Casorati, G, Porcelli, S, de la Salle, H, Mori, L, De Libero, G, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Antigens, CD1, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Antigens, CD1, Mice, 0302 clinical medicine, MESH: Gram-Negative Bacterial Infections, MESH: Glycolipids, MESH: Animals, Receptor, ComputingMilieux_MISCELLANEOUS, MESH: Immunity, CD1 restriction, lipid transfer proteins, natural killer T cells, Antigen Presentation, 0303 health sciences, Multidisciplinary, MESH: Kinetics, MESH: Dendritic Cells, biology, hemic and immune systems, Biological Sciences, Natural killer T cell, Lipids, Biochemistry, CD1D, lipids (amino acids, peptides, and proteins), Plant lipid transfer proteins, MESH: Mice, Transgenic, Antigen presentation, MESH: Glycoproteins, CD1, Mice, Transgenic, chemical and pharmacologic phenomena, Sphingomonas, 03 medical and health sciences, Immune system, Glycolipid, MESH: Sphingomonas, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, Glycoproteins, 030304 developmental biology, MESH: Humans, MESH: Clone Cells, Immunity, Dendritic Cells, MESH: Lipids, Clone Cells, Kinetics, MESH: Natural Killer T-Cells, MESH: Antigen Presentation, biology.protein, Natural Killer T-Cells, Glycolipids, Gram-Negative Bacterial Infections, 030215 immunology
Abstract: CD1e is a member of the CD1 family that participates in lipid antigen presentation without interacting with the T-cell receptor. It binds lipids in lysosomes and facilitates processing of complex glycolipids, thus promoting editing of lipid antigens. We find that CD1e may positively or negatively affect lipid presentation by CD1b, CD1c, and CD1d. This effect is caused by the capacity of CD1e to facilitate rapid formation of CD1–lipid complexes, as shown for CD1d, and also to accelerate their turnover. Similar results were obtained with antigen-presenting cells from CD1e transgenic mice in which lipid complexes are assembled more efficiently and show faster turnover than in WT antigen-presenting cells. These effects maximize and temporally narrow CD1-restricted responses, as shown by reactivity to Sphingomonas paucimobilis -derived lipid antigens. CD1e is therefore an important modulator of both group 1 and group 2 CD1-restricted responses influencing the lipid antigen availability as well as the generation and persistence of CD1–lipid complexes.
Published: 2011

4. TCR-inducible PLZF transcription factor required for innate phenotype of a subset of γδ T cells with restricted TCR diversity

Author: Roderick T. Bronson, Adam K. Savage, Harald von Boehmer, Taras Kreslavsky, Pablo Pereira, Fotini Gounari, Pier Paolo Pandolfi, Robin M. Hobbs, Albert Bendelac, Laboratory of Lymphocyte Biology, Dana-Farber Cancer Institute [Boston], Committe on Immunology, Howard Hughes Medical Institute (HHMI)-Department of pathology, Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine, University of Chicago, Rodent Histopathology Laboratory, Harvard Medical School [Boston] (HMS), Développement des Lymphocytes, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH: Spleen, T-Lymphocytes, medicine.medical_treatment, Dermatitis, MESH: Flow Cytometry, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, Mice, 0302 clinical medicine, Immunophenotyping, T-Lymphocyte Subsets, Promyelocytic Leukemia Zinc Finger Protein, MESH: Animals, Mice, Knockout, 0303 health sciences, Multidisciplinary, medicine.diagnostic_test, MESH: Genetic Predisposition to Disease, Receptors, Antigen, T-Cell, gamma-delta, hemic and immune systems, Biological Sciences, Flow Cytometry, Natural killer T cell, Phenotype, Cell biology, Cytokine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Kruppel-Like Transcription Factors, MESH: Immunophenotyping, MESH: Mice, Transgenic, Transgene, Kruppel-Like Transcription Factors, Mice, Transgenic, chemical and pharmacologic phenomena, Thymus Gland, Biology, Flow cytometry, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Receptors, Antigen, T-Cell, gamma-delta, MESH: Homeodomain Proteins, medicine, Animals, Cell Lineage, Genetic Predisposition to Disease, MESH: Dermatitis, MESH: Mice, Transcription factor, 030304 developmental biology, Homeodomain Proteins, T-cell receptor, MESH: Thymus Gland, MESH: Cell Lineage, MESH: Male, Mice, Inbred C57BL, MESH: T-Lymphocytes, MESH: Natural Killer T-Cells, Immunology, Natural Killer T-Cells, MESH: Female, Spleen, 030215 immunology
Abstract: International audience; Some gammadelta and alphabeta T lymphocytes exhibit an "innate" phenotype associated with rapid cytokine responses. The PLZF transcription factor is essential for the innate phenotype of NKT cells. This report shows that PLZF is likewise responsible for the innate, NKT-like phenotype of Vgamma1+Vdelta6.3/Vdelta6.4+ cells. TCR cross-linking induced PLZF expression in all polyclonal immature gammadelta thymocytes, suggesting that agonist selection might be required for PLZF induction. Transgenic expression of Vgamma1Vdelta6.4 TCR was sufficient to support the development of large numbers of PLZF+ T cells, further supporting the importance of the TCR for PLZF induction. Interestingly, expression of this TCR transgene led to the development of spontaneous dermatitis.
Published: 2009

5. Human CD4+invariant NKT cells are involved in antibacterial immunity againstBrucella suisthrough CD1d-dependent but CD4-independent mechanisms

Author: Sherri Dudal, Stéphanie Bessoles, Virginie Lafont, Gurdyal S. Besra, Françoise Sanchez, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie et Pathologie Cellulaire Infectieuse, Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cytotoxicity, Immunologic, Fas Ligand Protein, Brucella suis, MESH: Interferon-gamma, Immunology, Population, MESH: Antigens, CD4, Brucellosis, Cell Degranulation, Microbiology, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Immune system, MESH: Brucellosis, Humans, Immunology and Allergy, Macrophage, Cytotoxic T cell, fas Receptor, MESH: Cytotoxicity, Immunologic, education, MESH: Brucella suis, 030304 developmental biology, 0303 health sciences, education.field_of_study, MESH: Humans, biology, Tumor Necrosis Factor-alpha, Macrophages, MESH: Macrophages, MESH: Interleukin-4, Natural killer T cell, MESH: Fas Ligand Protein, MESH: Antigens, CD95, MESH: Natural Killer T-Cells, MESH: Antigens, CD1d, MESH: Tumor Necrosis Factor-alpha, CD1D, CD4 Antigens, MESH: Cell Degranulation, biology.protein, Natural Killer T-Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Interleukin-4, Antigens, CD1d, CD8, 030215 immunology
Abstract: International audience; Human invariant NKT (iNKT) cells are a unique subset of T cells, which recognize glycolipids presented by the CD1d. Among the iNKT cells, several functionally distinct subsets have been characterized according to CD4 and/or CD8 co-receptor expression. The current study is focussed on the CD4(+) iNKT cell subset and its role in an anti-infectious response. We have examined the role of CD4(+) iNKT cells on the intracellular Brucella suis growth. Our results indicate that CD4(+) iNKT cells impair the intramacrophagic growth of Brucella. This inhibition is due to a combination of soluble and contact-dependent mechanisms: IFN-gamma is weakly involved while cytotoxic activities such as the induction of the Fas pathway and the release of lytic granules are major mechanisms. The impairment of Brucella growth by CD4(+) iNKT cells requires an interaction with CD1d on macrophage surface. Also, we have shown that although CD4 regulates several biological responses of CD4(+) iNKT cells, it is not involved in their antibacterial activity. Here, we have shown for the first time that the CD4(+) iNKT cell population has antibacterial activity and thus, participates directly in the elimination of bacteria and/or in the control of bacterial growth by killing infected cells.
Published: 2009

6. Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin

Author: Carmelo Luci, Dan R. Littman, Ana Reynders, Céline Cognet, Esperanza Anguiano, Jean Hardwigsen, Eric Vivier, Ivaylo I. Ivanov, Marc Dalod, Elena Tomasello, Laurent Chiche, Damien Chaussabel, Lionel Chasson, Jacques Banchereau, Immunité muqueuse et vaccination, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rostov State University, Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Baylor Institute for Immunology Research (BIIR), Baylor College of Medecine, New York University School of Medicine (NYU), The Kimmel Center for Biology and Medicine at the Skirball Institute and Howard Hughes Medical Institute, Hôpital de la Timone [CHU - APHM] (TIMONE), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Interleukins, MESH: Antigens, CD3, MESH: Mice, Mutant Strains, MESH: Interferon-gamma, MESH: Natural Cytotoxicity Triggering Receptor 1, CD3, Immunology, Biology, Interleukin 22, 03 medical and health sciences, 0302 clinical medicine, Dermis, MESH: Mice, Inbred C57BL, medicine, Immunology and Allergy, MESH: Animals, MESH: Receptors, Thyroid Hormone, MESH: Lymphocyte Activation, MESH: Mice, 030304 developmental biology, MESH: Receptors, Retinoic Acid, 0303 health sciences, Lamina propria, MESH: Humans, Innate immune system, Lymphokine-activated killer cell, MESH: Transcription Factors, MESH: Dermis, Natural killer T cell, Cell biology, Lymphatic system, medicine.anatomical_structure, MESH: Natural Killer T-Cells, MESH: Intestinal Mucosa, biology.protein, MESH: Peyer's Patches, MESH: Cell Division, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030215 immunology
Abstract: International audience; NKp46+CD3- natural killer lymphocytes isolated from blood, lymphoid organs, lung, liver and uterus can produce granule-dependent cytotoxicity and interferon-gamma. Here we identify in dermis, gut lamina propria and cryptopatches distinct populations of NKp46+CD3- cells with a diminished capacity to degranulate and produce interferon-gamma. In the gut, expression of the transcription factor RORgammat, which is involved in the development of lymphoid tissue-inducer cells, defined a previously unknown subset of NKp46+CD3- lymphocytes. Unlike RORgammat- lamina propria and dermis natural killer cells, gut RORgammat+NKp46+ cells produced interleukin 22. Our data show that lymphoid tissue-inducer cells and natural killer cells shared unanticipated similarities and emphasize the heterogeneity of NKp46+CD3- cells in innate immunity, lymphoid organization and local tissue repair.
Published: 2008

7. Invariant NKT cells regulate the CD8 T cell response during Theiler's virus infection

Author: Roland S. Liblau, Maria Leite-de-Moraes, Magali Mas, Lucie Beaudoin, Jean-François Bureau, Lennart T. Mars, Agnès Lehuen, Jan Bauer, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department Neuroimmunology, Medizinische Universität Wien = Medical University of Vienna-Center for Brain Research, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Centre National de la Recherche Scientifique (CNRS), the French MS society (ARSEP), the Midi-Pyrénées Region, and the Agence National de la Recherche (ANR-06-MIME), Medizinische Universität Wien = Medical University of Vienna-Center for Brain Research [Vienna, Austria], Medizinische Universität Wien = Medical University of Vienna, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Bos, Mireille, Centre de Physiopathologie de Toulouse Purpan ( CPTP ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Medical University of Vienna-Center for Brain Research, Cytokines, hématopoïèse et réponse immune ( CHRI ), Génétique fonctionnelle des Maladies infectieuses, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Central Nervous System, MESH: Inflammation, Mouse, MESH: Spleen, Encephalomyelitis, viruses, Neuroimmunology, Priming (immunology), MESH : Poliomyelitis, MESH: Lymph Nodes, MESH: T-Lymphocyte Subsets, Immune Privilege, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Epitope, Epitopes, Mice, T-Lymphocyte Subsets, Cytotoxic T cell, MESH: Animals, Immune Response, MESH : Lymph Nodes, Multidisciplinary, T Cells, MESH : Central Nervous System, virus diseases, Animal Models, MESH : CD8-Positive T-Lymphocytes, Natural killer T cell, MESH: CD8-Positive T-Lymphocytes, MESH : Mice, Transgenic, Innate Immunity, 3. Good health, medicine.anatomical_structure, MESH: Encephalomyelitis, Medicine, Research Article, MESH : Spleen, MESH: Epitopes, MESH: Mice, Transgenic, Immune Cells, T cell, Science, Immunology, Mice, Transgenic, MESH : Mice, Inbred C57BL, MESH : Epitopes, Biology, Model Organisms, Immune system, Theilovirus, MESH: Mice, Inbred C57BL, MESH : Mice, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, MESH: Central Nervous System, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Lymphocyte Activation, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Immunity to Infections, MESH: Mice, MESH : Lymphocyte Activation, MESH : Encephalomyelitis, Inflammation, MESH : Inflammation, T-cell receptor, Immunity, Immunoregulation, MESH : Theilovirus, Immunologic Subspecialties, medicine.disease, MESH : Natural Killer T-Cells, Virology, MESH : T-Lymphocyte Subsets, Mice, Inbred C57BL, MESH: Theilovirus, MESH: Natural Killer T-Cells, MESH: Poliomyelitis, Natural Killer T-Cells, Clinical Immunology, MESH : Animals, Lymph Nodes, Spleen, Poliomyelitis
Abstract: International audience; Invariant NKT cells are innate lymphocytes with a broad tissue distribution. Here we demonstrate that iNKT cells reside in the central nervous system (CNS) in the absence of inflammation. Their presence in the CNS dramatically augments following inoculation of C57Bl/6 mice with the neurotropic Theiler's murine encephalomyelitis virus (TMEV). At the peak of inflammation the cellular infiltrate comprises 45,000 iNKT cells for 1250 CD8 T cells specific for the immunodominant TMEV epitope. To study the interaction between these two T cell subsets, we infected both iNKT cell deficient Jα18(-/-) mice and iNKT cell enriched Vα14 transgenic mice with TMEV. The CD8 T cell response readily cleared TMEV infection in the iNKT cell deficient mice. However, in the iNKT cell enriched mice TMEV infection persisted and was associated with significant mortality. This was caused by the inhibition of the CD8 T cell response in the cervical lymph nodes and spleen after T cell priming. Taken together we demonstrate that iNKT cells reside in the CNS in the absence of inflammation and that their enrichment is associated with the inhibition of the anti-viral CD8 T cell response and an augmented mortality during acute encephalomyelitis.
Published: 2014

8. TRAIL but not FasL and TNFα, regulates IL-33 expression in murine hepatocytes during acute hepatitis

Author: Muhammad Imran Arshad, Sabrina Nabti, Annie L'Helgoualc'h, Michel Rauch, Claire Piquet-Pellorce, Christian Trautwein, Frédéric Ezan, Michel Samson, Agnès Lehuen, Francisco Javier Cubero, Catherine Lucas-Clerc, Jean-Philippe Girard, Solène Patrat-Delon, Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire de biochimie générale, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie et génétique du diabète de type 1, génétique multifactorielle en endocrinologie pédiatrique ( U986 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Medical Department III, University Hospital Aachen, Institut de pharmacologie et de biologie structurale ( IPBS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et génétique du diabète de type 1, génétique multifactorielle en endocrinologie pédiatrique (U986), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : RNA, Messenger, medicine.medical_treatment, Gene Expression, Galactosamine, MESH : Hepatocytes, Hepatitis, Animal, MESH : Fas Ligand Protein, Fas ligand, MESH: Antibodies, Monoclonal, TNF-Related Apoptosis-Inducing Ligand, MESH: Hepatocytes, MESH : TNF-Related Apoptosis-Inducing Ligand, Antibodies, Monoclonal, Murine-Derived, Mice, 0302 clinical medicine, MESH : Receptors, Tumor Necrosis Factor, Type I, MESH: Receptors, Tumor Necrosis Factor, Type II, Concanavalin A, MESH: Animals, MESH : Acute Lung Injury, MESH: Galactosamine, MESH : Concanavalin A, Liver injury, MESH: Receptors, Tumor Necrosis Factor, Type I, MESH : Tumor Necrosis Factor-alpha, 0303 health sciences, biology, MESH: Hepatitis, Animal, Antibodies, Monoclonal, Interleukin, MESH : Receptors, Tumor Necrosis Factor, Type II, Natural killer T cell, 3. Good health, Cytokine, Receptors, Tumor Necrosis Factor, Type I, 030220 oncology & carcinogenesis, MESH : Antibodies, Monoclonal, Tumor necrosis factor alpha, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: TNF-Related Apoptosis-Inducing Ligand, Fas Ligand Protein, MESH: Gene Expression, MESH: Interleukins, Acute Lung Injury, Primary Cell Culture, chemical and pharmacologic phenomena, MESH: Concanavalin A, MESH: Primary Cell Culture, 03 medical and health sciences, MESH : Mice, medicine, Animals, Receptors, Tumor Necrosis Factor, Type II, RNA, Messenger, MESH : Perforin, MESH : Primary Cell Culture, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, Hepatitis, Hepatology, MESH : Galactosamine, Perforin, Tumor Necrosis Factor-alpha, Interleukins, MESH: Acute Lung Injury, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Interleukin-33, medicine.disease, MESH : Natural Killer T-Cells, MESH: Fas Ligand Protein, MESH: Perforin, MESH : Gene Expression, MESH: Natural Killer T-Cells, MESH: Tumor Necrosis Factor-alpha, Immunology, Hepatocytes, biology.protein, Cancer research, Natural Killer T-Cells, MESH : Animals, MESH : Interleukins, MESH : Hepatitis, Animal
Abstract: International audience; UNLABELLED: Interleukin (IL)-33, a member of the IL-1 cytokine family, positively correlates with acute hepatitis and chronic liver failure in mice and humans. IL-33 is expressed in hepatocytes and is regulated by natural killer T (NKT) cells during concanavalin A (ConA)-induced acute liver injury. Here, we investigated the molecular mechanisms underlying the expression of IL-33 during acute hepatitis. The expression of IL-33 and its regulation by death receptor pathways was investigated after the induction of ConA-acute hepatitis in wildtype (WT), perforin(-/-) , tumor necrosis factor related apoptosis inducing ligand (TRAIL)(-/-) , and NKT cell-deficient (CD1d(-/-) ) mice. In addition, we used a model of acute liver injury by administering Jo2/Fas-antibody or D-galactosamine-tumor necrosis factor alpha (TNFα) in WT mice. Finally, the effect of TRAIL on IL-33 expression was assessed in primary cultured murine hepatocytes. We show that IL-33 expression in hepatocytes is partially controlled by perforin during acute liver injury, but not by TNFα or Fas ligand (FasL). Interestingly, the expression of IL-33 in hepatocytes is blocked during ConA-acute hepatitis in TRAIL-deficient mice compared to WT mice. In contrast, administration of recombinant murine TRAIL associated with ConA-priming in CD1d-deficient mice or in vitro stimulation of murine hepatocytes by TRAIL but not by TNFα or Jo2 induced IL-33 expression in hepatocytes. The IL-33-deficient mice exhibited more severe ConA liver injury than WT controls, suggesting a protective effect of IL-33 in ConA-hepatitis. CONCLUSION: The expression of IL-33 during acute hepatitis is dependent on TRAIL, but not on FasL or TNFα.
Published: 2012

9. Dok-1 overexpression promotes development of γδ natural killer T cells

Author: Gilles, Besin, Mitra, Yousefi, Ingrid, Saba, Roscoe, Klinck, Pier Paolo, Pandolfi, Pascale, Duplay, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Laboratoire de Génomique Fonctionnelle, Université de Sherbrooke (UdeS), Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS)-Harvard Medical School [Boston] (HMS)-Beth Israel Deaconess Cancer Center, and This work was supported by grants from the Canadian Institutes of Health Research (CIHR) to P.D. M.Y. and I. S. were partly supported by studentships from the Fondation Armand-Frappier
Subjects: CD4-Positive T-Lymphocytes, Male, MESH: Mice, Transgenic, Kruppel-Like Transcription Factors, Mice, Transgenic, CD8-Positive T-Lymphocytes, MESH: Phosphoproteins, Mice, MESH: Receptors, Antigen, T-Cell, gamma-delta, MESH: Mice, Inbred C57BL, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Intracellular Signaling Peptides and Proteins, Animals, Promyelocytic Leukemia Zinc Finger Protein, MESH: Animals, Signaling Lymphocytic Activation Molecule Associated Protein, MESH: Mice, Intracellular Signaling Peptides and Proteins, RNA-Binding Proteins, MESH: CD4-Positive T-Lymphocytes, Receptors, Antigen, T-Cell, gamma-delta, γδ Tcell Dok PLZF SAP Thymocyte development, Phosphoproteins, MESH: CD8-Positive T-Lymphocytes, MESH: Male, DNA-Binding Proteins, Mice, Inbred C57BL, MESH: RNA-Binding Proteins, MESH: Natural Killer T-Cells, Natural Killer T-Cells, Female, MESH: Kruppel-Like Transcription Factors, MESH: Female, MESH: DNA-Binding Proteins
Abstract: International audience; In T cells, two members of the Dok family, Dok-1 and Dok-2, are predominantly expressed. Recent evidence suggests that they play a negative role in T-cell signaling. In order to define whether Dok proteins regulate T-cell development, we have generated transgenic mice overexpressing Dok-1 in thymocytes and peripheral T cells. We show that overexpression of Dok-1 retards the transition from the CD4(-) CD8(-) to CD4(+) CD8(+) stage. Moreover, there is a specific expansion of PLZF-expressing Vγ1.1(+) Vδ6.3(+) T cells. This subset of γδ T cells acquires innate characteristics including rapid IL-4 production following stimulation and requiring SLAM-associated adaptor protein (SAP) for their development. Moreover, Dok-1 overexpression promotes the generation of an innate-like CD8(+) T-cell population that expresses Eomesodermin. Altogether, these findings identify a novel role for Dok-1 in the regulation of thymic differentiation and in particular, in the development of PLZF(+) γδ T cells.
Published: 2012

10. Key role for respiratory CD103(+) dendritic cells, IFN-γ, and IL-17 in protection against Streptococcus pneumoniae infection in response to α-galactosylceramide

Author: Laurye Van Maele, Jean-Claude Sirard, Hélène Léger, Bernard Ryffel, Christelle Faveeuw, Stoyan Ivanov, Elodie Macho Fernandez, Natalia Muñoz Wolf, Analía Rial, Christophe Paget, Arndt Benecke, Joelle Renneson, Benoît Frisch, François Trottein, José A. Chabalgoity, Isabelle Maillet, Josette Fontaine, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universidad de la República [Montevideo] (UDELAR), Institut des Hautes Études Scientifiques (IHES), IHES, Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale, CNRS,University of Lille Nord de France, Institut Pasteur de Lille, évaluation-orientation de la coopération scientifique (ECOS)-Sud [U08S02], and Institut National du Cancer (INCa, projets libres 2008) under reference R08046EE/RPT08003EEA and Agence Nationale de la recherche (ANR) under reference ANR-08-MIEN-021-01 [R08066ES RPV08036ESA]. SI, CP and EMF were recipients of a doctoral fellowship from the Ministère de l'Education Nationale de la Recherche et Technique (SI and EMF) and the Conseil Régional Nord Pas de Calais/Inserm (CP). CF and JCS are supported by Inserm and BR, AB, and FT by the CNRS., Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Universidad de la República [Montevideo] (UCUR), Institut des Hautes Etudes Scientifiques (IHES), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé-Université de Lille, Sciences et Technologies, and Sirard, Jean-Claude
Subjects: MESH: Signal Transduction, Male, MESH: Interleukin-17, Kaplan-Meier Estimate, medicine.disease_cause, Mice, 0302 clinical medicine, Immunology and Allergy, Macrophage, MESH: Animals, MESH: Pneumococcal Infections, MESH: Antigens, CD, 0303 health sciences, education.field_of_study, MESH: Dendritic Cells, Interleukin-17, MESH: Galactosylceramides, 3. Good health, Pneumococcal infections, Infectious Diseases, medicine.anatomical_structure, Streptococcus pneumoniae, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, Interleukin 17, Bronchoalveolar Lavage Fluid, Integrin alpha Chains, MESH: Streptococcus pneumoniae, Signal Transduction, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Interferon-gamma, Population, chemical and pharmacologic phenomena, Galactosylceramides, Biology, Pneumococcal Infections, Microbiology, 03 medical and health sciences, Interferon-gamma, Antigen, MESH: Mice, Inbred C57BL, Antigens, CD, medicine, Animals, education, MESH: Mice, MESH: Kaplan-Meier Estimate, 030304 developmental biology, Innate immune system, Lung, MESH: Bronchoalveolar Lavage Fluid, MESH: Integrin alpha Chains, Dendritic Cells, medicine.disease, MESH: Male, Immunity, Innate, Mice, Inbred C57BL, MESH: Natural Killer T-Cells, Immunology, Natural Killer T-Cells, 030215 immunology
Abstract: International audience; BACKGROUND: Exogenous activation of pulmonary invariant natural killer T (iNKT) cells, a population of lipid-reactive αβ T lymphocytes, with use of mucosal α-galactosylceramide (α-GalCer) administration, is a promising approach to control respiratory bacterial infections. We undertook the present study to characterize mechanisms leading to α-GalCer-mediated protection against lethal infection with Streptococcus pneumoniae serotype 1, a major respiratory pathogen in humans. METHODS AND RESULTS: α-GalCer was administered by the intranasal route before infection with S. pneumoniae. We showed that respiratory dendritic cells (DCs), most likely the CD103(+) subset, play a major role in the activation (IFN-γ and IL-17 release) of pulmonary iNKT cells, whereas alveolar and interstitial macrophages are minor players. After challenge, S. pneumoniae was rapidly (4 hours) eliminated in the alveolar spaces, a phenomenon that depended on respiratory DCs and neutrophils, but not macrophages, and on the early production of both IFN-γ and IL-17. Protection was also associated with the synthesis of various interferon-dependent and IL-17-associated genes as revealed by transcriptomic analysis. CONCLUSIONS: These data imply a new function for pulmonary CD103(+) DCs in mucosal activation of iNKT cells and establish a critical role for both IFN-γ and IL-17 signalling pathways in mediating the innate immune response to S. pneumoniae.
Published: 2012

11. Identification of invariant natural killer T cells in porcine peripheral blood

Author: Jean-Marc Gombert, Antoine Thierry, S. Minouflet, Guy Touchard, Aurélie Robin, A Herbelin, Anne Barra, Thierry Hauet, Sébastien Giraud, Franck Bridoux, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hauet, Thierry
Subjects: Male, MESH: Immunophenotyping, Swine, CD3, Immunology, Cell, MESH: Flow Cytometry, Galactosylceramides, Statistics, Nonparametric, Immunophenotyping, 03 medical and health sciences, 0302 clinical medicine, Antigen, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Swine, 030304 developmental biology, 0303 health sciences, MESH: Statistics, Nonparametric, MESH: Cytokines, Innate immune system, General Veterinary, biology, MESH: Galactosylceramides, Flow Cytometry, Phenotype, In vitro, MESH: Male, Immunity, Innate, Cell biology, MESH: Leukocytes, Mononuclear, medicine.anatomical_structure, MESH: Natural Killer T-Cells, MESH: Antigens, CD1d, CD1D, biology.protein, Leukocytes, Mononuclear, Cytokines, Natural Killer T-Cells, MESH: Immunity, Innate, Antigens, CD1d, CD8, 030215 immunology
Abstract: International audience; The pig is a relevant preclinical model for numerous pathologies used to validate therapeutic strategies for translation to human. Although invariant natural killer T (iNKT) lymphocytes are a component of innate immunity implicated in many pathological processes, little is known on their characterization in swine. By addressing this issue using mouse α-galactosylceramide-loaded CD1d tetramers (α-GC-CD1dTT), which are commonly used to track iNKT cells, we were able to unequivocally identify CD3(+)α-GC-CD1dTT(+) cells in porcine peripheral blood, hereafter referred to as swine iNKT cells. These lymphocytes are enriched in CD4(-)CD8(+) and CD4(-)CD8(-) cells, harbor an activated-memory phenotype (SLA-DR(+)CD45RA(-)), express the intracellular promyelocytic-leukemia-zinc-finger (PLZF) transcription factor and are significantly enriched in IFN-γ-producing cells after in vitro activation in comparison with conventional T cells. Importantly, in presence of IL-2 and IL-15, the iNKT cell ligand α-GC induces selective expansion of CD3(+)α-GC-CD1dTT(+) cells, confirming the reactivity of swine iNKT cells against α-GC. When associated with α-GC, IL-33, an alarmin of IL-1 family recently described to target iNKT cells, leads to a greater expansion of CD3(+)α-GC-CD1dTT(+) cells than IL-2 and IL-15. Altogether, our results provide the first phenotypic and functional description of swine iNKT cells allowing to further study the critical role of iNKT cells in porcine models of organ injury.
Published: 2012

12. NKT cells are required to induce high IL-33 expression in hepatocytes during ConA-induced acute hepatitis

Author: Michel Rauch, Muhammad Imran Arshad, Michel Samson, Maria Leite-de-Moraes, Valérie Julia, Catherine Lucas-Clerc, Claire Piquet-Pellorce, Annie L'Helgoualc'h, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie générale, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], INSERM, Ministère de l'Education Nationale de la Recherche et de la Technologie, University de Rennes 1, Région Bretagne, National French Society of Gastro-Enterology (SNFGE), Ligue contre le cancer, IFR 140, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA), Signalisation et Réponses aux Agents Infectieux et Chimiques ( SeRAIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Male, medicine.medical_treatment, Fluorescent Antibody Technique, MESH : Carbon Tetrachloride, MESH: Flow Cytometry, MESH : Hepatocytes, MESH: Hepatocytes, Mice, 0302 clinical medicine, MESH: Interleukin-1beta, Concanavalin A, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Fluorescent Antibody Technique, 0303 health sciences, MESH : Acute Disease, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH: Hepatitis, Animal, Flow Cytometry, Natural killer T cell, Adoptive Transfer, 3. Good health, NKT cells, Alarmin, CD1D, Acute Disease, MESH: Acute Disease, Tumor necrosis factor alpha, MESH : Antigens, CD1d, MESH: Interleukins, MESH: Gene Expression, Immunology, MESH: Concanavalin A, MESH : Interleukin-1beta, 03 medical and health sciences, Tumor Necrosis Factor-alpha, Interleukins, MESH: Carbon Tetrachloride, Interleukin-33, medicine.disease, MESH: Interleukin-6, MESH : Gene Expression, MESH : Fluorescent Antibody Technique, MESH: Adoptive Transfer, MESH: Antigens, CD1d, MESH: Tumor Necrosis Factor-alpha, Natural Killer T-Cells, MESH : Hepatitis, Animal, MESH: Female, MESH: Liver, Adoptive cell transfer, Interleukin-1beta, Gene Expression, Hepatitis, Animal, MESH: Mice, Knockout, Hepatitis, MESH: Reverse Transcriptase Polymerase Chain Reaction, Immunology and Allergy, MESH : Female, Carbon Tetrachloride, MESH : Concanavalin A, Mice, Knockout, MESH : Tumor Necrosis Factor-alpha, Mice, Inbred BALB C, biology, Reverse Transcriptase Polymerase Chain Reaction, MESH : Adoptive Transfer, Cytokine, Liver, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Interleukin-6, MESH : Flow Cytometry, MESH : Male, MESH: Mice, Inbred BALB C, chemical and pharmacologic phenomena, MESH : Mice, medicine, Animals, MESH: Mice, MESH : Mice, Inbred BALB C, 030304 developmental biology, Interleukin-6, MESH : Liver, MESH : Natural Killer T-Cells, Molecular biology, MESH: Male, Interleukin 33, MESH: Natural Killer T-Cells, Hepatocytes, biology.protein, IL-33, MESH : Mice, Knockout, MESH : Animals, Antigens, CD1d, MESH : Interleukins, 030215 immunology
Abstract: International audience; Interleukin-33 (IL-33) is thought to be released during cellular death as an alarming cytokine during the acute phase of disease, but its regulation in vivo is poorly understood. We investigated the expression of IL-33 in two mouse models of acute hepatitis by administering either carbon tetrachloride (CCl(4) ) or concanavalin A (ConA). IL-33 was overexpressed in both models but with a stronger induction in ConA-induced hepatitis. IL-33 was weakly expressed in vascular and sinusoidal endothelial cells from normal liver and was clearly induced in CCl(4) -treated mice. Surprisingly, we found that hepatocytes strongly expressed IL-33 exclusively in the ConA model. CD1d knock-out mice, which are deficient in NKT cells and resistant to ConA-induced hepatitis, no longer expressed IL-33 in hepatocytes following ConA administration. Interestingly, invariant NKT (iNKT) cells adoptively transferred into ConA-treated CD1d KO mouse restored IL-33 expression in hepatocytes. This strongly suggests that NKT cells are responsible for the induction of IL-33 in hepatocytes.
Published: 2011

13. Invariant natural killer T-cell-deficient mice display increased CCl₄ -induced hepatitis associated with CXCL1 over-expression and neutrophil infiltration

Author: Lisbonne, Mariette, L'Helgoualc'H, Annie, Nauwelaers, Gwendoline, Turlin, Bruno, Lucas, Catherine, Herbelin, André, Piquet-Pellorce, Claire, Samson, Michel, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), departement de pathologie, Laboratoire de biochimie générale, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, Signalisation et Réponses aux Agents Infectieux et Chimiques ( SeRAIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes (UR), and CHU Pontchaillou [Rennes]
Subjects: CXCL1/KC, Neutrophils, Chemokine CXCL1, Receptors, Antigen, T-Cell, alpha-beta, MESH : Carbon Tetrachloride, Apoptosis, MESH : Hepatocytes, Hepatitis, Animal, MESH: Neutrophils, MESH: Mice, Knockout, Hepatitis, MESH : Neutrophils, MESH: Hepatocytes, Mice, Cell Movement, MESH : Cell Movement, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Matrix Metalloproteinase 8, Carbon Tetrachloride, MESH: Cell Movement, Cells, Cultured, Mice, Knockout, Alanine, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH : Acute Disease, Neutrophil, MESH: Hepatitis, Animal, MESH : Chemokine CXCL1, Matrix Metalloproteinase 8, MESH : Receptors, Antigen, T-Cell, alpha-beta, Liver, Acute Disease, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Cells, Cultured, MESH: Alanine, MESH : Aspartate Aminotransferases, MESH: Aspartate Aminotransferases, MESH : Mice, MESH : Cells, Cultured, Animals, MESH: Chemokine CXCL1, Aspartate Aminotransferases, MESH: Mice, MESH: Apoptosis, MESH: Carbon Tetrachloride, MESH : Liver, MESH : Natural Killer T-Cells, MESH: Natural Killer T-Cells, MESH: Matrix Metalloproteinase 8, Hepatocytes, Invariant NKT cells, MESH : Mice, Knockout, Natural Killer T-Cells, MESH : Animals, MESH : Alanine, MESH : Hepatitis, Animal, MESH : Apoptosis, MESH: Liver
Abstract: International audience; Invariant natural killer T (iNKT) cells are involved in the intrahepatic immune response and in hepatitis. In particular, iNKT lymphocytes are responsible for hepatocyte death in concanavalin A-induced hepatitis in mice. We examined the role of iNKT cells in acute hepatitis induced by a hepatotoxic agent, carbon tetrachloride (CCl(4) ). WT and iNKT cell-deficient (Jα18(-/-) ) mice were challenged with a single dose of 2.4 g/kg CCl(4) and both hepatic physiopathology and immune responses were studied. Plasma alanine and aspartate amino-transferase levels were significantly higher in Jα18(-/-) mice than in WT mice two days after CCl(4) administration. Chemokine CXCL1/keratinocyte-derived chemokine (KC) and MMP-8 were significantly higher in iNKT cell-deficient mice than in control mice. The more severe liver injury in Jα18(-/-) mice was associated with greater leukocyte infiltrate, which was enriched in neutrophils (CD11b(+) CD11c(-) Gr-1(+) cells), in agreement with CXCL1/KC and MMP-8 levels. Complementary experiments with NK-depleted animals indicate a minor role for NK cells in the liver damage found in iNKT-deficient mice. Thus, unlike for ConA-induced hepatitis, we report that iNKT cells protect the liver against acute hepatitis induced by CCl(4) and limit neutrophil infiltration.
Published: 2011

14. Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay

Author: Agnès Lehuen, Roberto Mallone, Marc Dalod, Lucie Beaudoin, Julien Diana, Anna Tafuri, Vedran Brezar, Christian Boitard, Andrew L. Mellor, Matthias von Herrath, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medical College of Georgia, Immunotherapy Center, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), CHU Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), La Jolla Institute for Allergy and Immunology (LIA), La Jolla Institute for Allergy & Immunology, Université Paris Descartes - Paris 5 ( UPD5 ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and La Jolla Institute for Allergy and Immunology ( LIA )
Subjects: MESH: Interleukin-10, endocrine system diseases, Programmed Cell Death 1 Receptor, MESH: Membrane Glycoproteins, MESH : Membrane Glycoproteins, MESH: Lymph Nodes, Cell Communication, CD8-Positive T-Lymphocytes, Lymphocyte Activation, T-Lymphocytes, Regulatory, B7-H1 Antigen, MESH : Diabetes Mellitus, Type 1, MESH : T-Lymphocytes, Regulatory, Interleukin 21, Mice, 0302 clinical medicine, Transforming Growth Factor beta, immune system diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, IL-2 receptor, MESH : Antigens, CD80, MESH : Lymph Nodes, 0303 health sciences, Membrane Glycoproteins, MESH: Dendritic Cells, MESH : Peptides, MESH: Peptides, FOXP3, hemic and immune systems, MESH : CD8-Positive T-Lymphocytes, Natural killer T cell, MESH: CD8-Positive T-Lymphocytes, 3. Good health, Interleukin-10, MESH: Virus Diseases, medicine.anatomical_structure, Virus Diseases, Antigens, Surface, B7-1 Antigen, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Diabetes Mellitus, Type 1, MESH : Apoptosis Regulatory Proteins, MESH : Antigens, Surface, endocrine system, MESH : Cell Communication, MESH: Antigens, Surface, T cell, Immunology, macromolecular substances, Biology, Article, 03 medical and health sciences, Islets of Langerhans, MESH: Antigens, CD80, MESH : Interleukin-10, MESH : Mice, MESH: Cell Communication, medicine, Animals, MESH : Islets of Langerhans, Antigen-presenting cell, MESH: Lymphocyte Activation, MESH: Mice, MESH : Lymphocyte Activation, MESH: Transforming Growth Factor beta, 030304 developmental biology, MESH: Apoptosis Regulatory Proteins, MESH: T-Lymphocytes, Regulatory, MESH: Islets of Langerhans, Dendritic cell, Dendritic Cells, MESH : Virus Diseases, MESH : Natural Killer T-Cells, MESH : Transforming Growth Factor beta, Diabetes Mellitus, Type 1, MESH: Natural Killer T-Cells, MESH : Dendritic Cells, Natural Killer T-Cells, MESH : Animals, Lymph Nodes, Apoptosis Regulatory Proteins, Peptides, 030215 immunology
Abstract: iNKT cell and pDC cross talk prevents type 1 diabetes by inducing T reg cells in the pancreatic lymph node during viral infection., Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell–mediated destruction of insulin-producing β cells, and viral infections can prevent the onset of disease. Invariant natural killer T cells (iNKT cells) exert a regulatory role in T1D by inhibiting autoimmune T cell responses. As iNKT cell–plasmacytoid dendritic cell (pDC) cooperation controls viral replication in the pancreatic islets, we investigated whether this cellular cross talk could interfere with T1D development during viral infection. Using both virus-induced and spontaneous mouse models of T1D, we show that upon viral infection, iNKT cells induce TGF-β–producing pDCs in the pancreatic lymph nodes (LNs). These tolerogenic pDCs convert naive anti-islet T cells into Foxp3+ CD4+ regulatory T cells (T reg cells) in pancreatic LNs. T reg cells are then recruited into the pancreatic islets where they produce TGF-β, which dampens the activity of viral- and islet-specific CD8+ T cells, thereby preventing T1D development in both T1D models. These findings reveal a crucial cooperation between iNKT cells, pDCs, and T reg cells for prevention of T1D by viral infection.
Published: 2011

15. Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of peripheral lymph node NK1.1- invariant NKT cells to bacteria

Author: Pauline Henrot, Latiffa Amniai, Colin Havenar-Daughton, Jean-Marc Doisne, Chantal Bécourt, Valérie Soulard, Isabelle Couillin, Charlène Blanchet, Kamel Benlagha, Jean-Marc Cavaillon, Laurence Zitvogel, Bernhard Ryffel, Julien C. Marie, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Medicine, Université Paris-Sud - Paris 11 (UP11), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Cytokines et Inflammation, Institut Pasteur [Paris], Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris] (IP)
Subjects: MESH: Signal Transduction, Receptors, Retinoic Acid, MESH: Interleukin-17, Interleukin-1beta, Retinoic acid, MESH: Lymph Nodes, Interleukin-23, MESH: Mice, Knockout, chemistry.chemical_compound, Mice, 0302 clinical medicine, MESH: Interleukin-1beta, MESH: Staphylococcus aureus, Immunology and Allergy, Antigens, Ly, MESH: Animals, Cells, Cultured, Orphan receptor, Mice, Knockout, MESH: Interleukin-23, 0303 health sciences, MESH: Escherichia coli, Interleukin-17, MESH: Antigens, Ly, Natural killer T cell, 3. Good health, Cell biology, MESH: NK Cell Lectin-Like Receptor Subfamily B, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, Interleukin 17, NK Cell Lectin-Like Receptor Subfamily B, Signal Transduction, MESH: Cells, Cultured, Staphylococcus aureus, MESH: Interleukins, Immunology, Biology, 03 medical and health sciences, Downregulation and upregulation, MESH: Mice, Inbred C57BL, Escherichia coli, Animals, MESH: Mice, 030304 developmental biology, MESH: Receptors, Retinoic Acid, Interleukins, In vitro, Immunity, Innate, Mice, Inbred C57BL, TLR2, chemistry, MESH: Natural Killer T-Cells, Natural Killer T-Cells, MESH: Dendritic Cells, Follicular, Lymph Nodes, Peripheral lymph, Dendritic Cells, Follicular, 030215 immunology
Abstract: We have shown previously that peripheral lymph node-resident retinoic acid receptor-related orphan receptor γt+ NK1.1− invariant NKT (iNKT) cells produce IL-17A independently of IL-6. In this study, we show that the concomitant presence of IL-1 and IL-23 is crucial to induce a rapid and sustained IL-17A/F and IL-22 response by these cells that requires TCR–CD1d interaction and partly relies on IL-23–mediated upregulation of IL-23R and IL-1R1 expression. We further show that IL-1 and IL-23 produced by pathogen-associated molecular pattern-stimulated dendritic cells induce this response from NK1.1− iNKT cells in vitro, involving mainly TLR2/4-signaling pathways. Finally, we found that IL-17A production by these cells occurs very early and transiently in vivo in response to heat-killed bacteria. Overall, our study indicates that peripheral lymph node NK1.1− iNKT cells could be a source of innate Th17-related cytokines during bacterial infections and supports the hypothesis that they are able to provide an efficient first line of defense against bacterial invasion.
Published: 2011

16. Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions

Author: Gérard Eberl, Kamel Benlagha, Jean-Marc Doisne, Nádia Duarte, Jean-Benoît Le Luduec, Latiffa Amniai, Chantal Bécourt, Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Immunité infection vaccination ( I2V ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: MESH: Nuclear Receptor Subfamily 1, Group F, Member 3, MESH: Inflammation, Receptors, Retinoic Acid, MESH: Interleukin-17, Retinoic acid, MESH: Lymph Nodes, C-C chemokine receptor type 6, MESH: Mice, Knockout, chemistry.chemical_compound, Mice, 0302 clinical medicine, MESH : Cell Proliferation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, MESH: Animals, MESH : Lymph Nodes, Skin, Orphan receptor, Mice, Knockout, 0303 health sciences, education.field_of_study, Receptors, Thyroid Hormone, Interleukin-17, MESH: Galactosylceramides, MESH : Receptors, Thyroid Hormone, hemic and immune systems, Nuclear Receptor Subfamily 1, Group F, Member 3, Natural killer T cell, MESH : Receptors, Retinoic Acid, MESH : Epithelial Cells, MESH: Epithelial Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Nuclear Receptor Subfamily 1, Group F, Member 3, Interleukin 17, MESH : Interleukin-6, Immunology, Population, Galactosylceramides, MESH : Interleukin-17, Biology, 03 medical and health sciences, Immune system, MESH: Skin, MESH: Cell Proliferation, MESH : Mice, MESH : Skin, Animals, MESH: Receptors, Thyroid Hormone, education, MESH: Mice, 030304 developmental biology, Cell Proliferation, MESH: Receptors, Retinoic Acid, Inflammation, MESH : Inflammation, Interleukin-6, Epithelial Cells, MESH : Natural Killer T-Cells, MESH: Interleukin-6, Retinoic acid receptor, MESH: Natural Killer T-Cells, chemistry, Cancer research, MESH : Mice, Knockout, Natural Killer T-Cells, MESH : Animals, Lymph Nodes, MESH : Galactosylceramides, 030215 immunology
Abstract: Lymph nodes (LNs) have been long considered as comprising few invariant NKT (iNKT) cells, and these cells have not been studied extensively. In this study, we unravel the existence of stable rather than transitional LN-resident NK1.1(-) iNKT cell populations. We found the one resident in peripheral LNs (PLNs) to comprise a major IL-17-producing population and to express the retinoic acid receptor-related orphan receptor (gamma)t (ROR(gamma)t). These cells respond to their ligand alpha-galactosylceramide (alpha-GalCer) in vivo by expanding dramatically in the presence of LPS, providing insight into how this rare population could have an impact in immune responses to infection. PLN-resident ROR(gamma)t(+) NK1.1(-) iNKT cells express concomitantly CCR6, the integrin alpha-chain alpha(E) (CD103), and IL-1R type I (CD121a), indicating that they might play a role in inflamed epithelia. Accordingly, skin epithelia comprise a major ROR(gamma)t(+) CCR6(+)CD103(+)CD121a(+) NK1.1(-) cell population, reflecting iNKT cell composition in PLNs. Importantly, both skin and draining PLN ROR(gamma)t(+) iNKT cells respond preferentially to inflammatory signals and independently of IL-6, indicating that they could play a nonredundant role during inflammation. Overall, our study indicates that ROR(gamma)t(+) iNKT cells could play a major role in the skin during immune responses to infection and autoimmunity.
Published: 2009

17. iNKT cell development is orchestrated by different branches of TGF-beta signaling

Author: Sylvie Martel, C Garcia, Régine Losson, Jean-Marc Doisne, Farhan S. Cyprian, Nadia Duarte, Kamel Benlagha, Kai-Ping Yan, Jean-Benoît Le Luduec, Laurent Bartholin, Julien C. Marie, Branka Horvat, David F. Vincent, Ruth Rimokh, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP], Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de génétique et biologie moléculaire et cellulaire ( IGBMC ), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), École normale supérieure - Lyon ( ENS Lyon ) -IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunité infection vaccination ( I2V ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), and Peney, Maité
Subjects: MESH: Signal Transduction, MESH : Transcription Factors, MESH : Receptors, Transforming Growth Factor beta, MESH: Spleen, Cellular differentiation, Apoptosis, MESH: T-Lymphocyte Subsets, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Transforming Growth Factor beta, MESH: Smad4 Protein, Immunology and Allergy, MESH: Animals, Smad4 Protein, 0303 health sciences, biology, Stem Cells, Cell Differentiation, MESH: Transcription Factors, Natural killer T cell, MESH : Mice, Transgenic, Cell biology, MESH: Interleukin-2 Receptor beta Subunit, MESH : Stem Cells, MESH: Receptors, Transforming Growth Factor beta, Stem cell, Signal transduction, MESH : Cell Differentiation, Signal Transduction, MESH : Spleen, MESH: Cell Differentiation, MESH: T-Box Domain Proteins, MESH: Mice, Transgenic, Immunology, MESH : Cell Lineage, Mice, Transgenic, MESH: Stem Cells, Article, 03 medical and health sciences, MESH : Mice, TGF beta signaling pathway, Animals, Cell Lineage, Transcription factor, MESH: Mice, MESH: Transforming Growth Factor beta, MESH : Interleukin-2 Receptor beta Subunit, 030304 developmental biology, MESH : Signal Transduction, Cell growth, MESH: Apoptosis, MESH : Smad4 Protein, Transforming growth factor beta, MESH: Cell Lineage, MESH : Natural Killer T-Cells, MESH : T-Lymphocyte Subsets, Interleukin-2 Receptor beta Subunit, MESH : T-Box Domain Proteins, MESH : Transforming Growth Factor beta, MESH: Natural Killer T-Cells, biology.protein, Natural Killer T-Cells, MESH : Animals, T-Box Domain Proteins, Receptors, Transforming Growth Factor beta, Spleen, MESH : Apoptosis, Transcription Factors, 030215 immunology
Abstract: International audience; Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-beta controls the differentiation program of iNKT cells. We demonstrate that TGF-beta signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-beta involves the concerted action of different pathways of TGF-beta signaling. Whereas the Tif-1gamma branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1gamma/Smad4-independent branch. Thus, these three different branches of TGF-beta signaling function in concert as complementary effectors, allowing TGF-beta to fine tune the iNKT cell differentiation program.
Published: 2009

18. The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-gamma production

Author: Michel Samson, Elvire Bourgeois, Pierre Gourdy, Séverine Diem, Stéphane Roga, Elke Schneider, Michel Dy, Linh Pham Van, Jean-Philippe Girard, Anne Barra, André Herbelin, Jean-Marc Gombert, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Détoxication et réparation tissulaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Laboratoire d'immunologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CNRS, Université de Paris Descartes, Ligue Nationale contre le Cancer, la Chancellerie des Universités de Paris, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Slama, Catherine, Université de Rennes (UR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Signalisation et Réponses aux Agents Infectieux et Chimiques ( SeRAIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Institut de pharmacologie et de biologie structurale ( IPBS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Interleukin-12, MESH: Spleen, medicine.medical_treatment, MESH: Mice, Knockout, Interleukin 21, Mice, 0302 clinical medicine, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH: Animals, IL-2 receptor, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, 0303 health sciences, Mice, Inbred BALB C, ZAP70, Natural killer T cell, Interleukin-12, Killer Cells, Natural, Cytokine, Liver, Interleukin 12, Cytokines, Natural killer cells, Natural killer T cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Killer Cells, Natural, MESH : Spleen, MESH: Killer Cells, Natural, MESH: Interleukins, MESH: Interferon-gamma, Immunology, MESH: Mice, Inbred BALB C, MESH : Mice, Inbred C57BL, Biology, MESH : Interleukin-4, 03 medical and health sciences, Interferon-gamma, Th2 Cells, MESH: Mice, Inbred C57BL, MESH: Th2 Cells, MESH : Mice, medicine, MESH : Interleukin-12, Animals, Humans, MESH: Mice, MESH : Mice, Inbred BALB C, MESH : Interferon-gamma, 030304 developmental biology, Inflammation, Lymphokine-activated killer cell, MESH: Humans, Interleukins, MESH : Humans, MESH : Liver, MESH: Interleukin-4, Interleukin-33, MESH : Natural Killer T-Cells, MESH : Th2 Cells, Interleukin 33, Mice, Inbred C57BL, MESH: Natural Killer T-Cells, Natural Killer T-Cells, MESH : Mice, Knockout, Th1/Th2 cells, Interleukin-4, MESH : Animals, MESH : Interleukins, MESH: Female, Spleen, 030215 immunology, MESH: Liver
Abstract: International audience; IL-33 has recently been identified as a cytokine endowed with pro-Th2 functions, raising the question of its effect on invariant natural killer T cell (iNKT), which are potent IL-4 producers. Here, we report a two-fold increase of iNKT-cell counts in spleen and liver after a 7-day treatment of mice with IL-33, which results from a direct effect, given that purified iNKT cells express the T1/ST2 receptor constitutively and respond to IL-33 by in vitro expansion and functional activation. Conversely to the expected pro-Th2 effect, IL-33 induced a preferential increase in IFN-gamma rather than IL-4 production upon TCR engagement that depended on endogenous IL-12. Moreover, in combination with the pro-inflammatory cytokine IL-12, IL-33 enhanced IFN-gamma production by both iNKT and NK cells. Taken together these data support the conclusion that IL-33 can contribute as a co-stimulatory factor to innate cellular immune responses.
Published: 2009

19. Stepwise development of MAIT cells in mouse and human

Author: Claire Soudais, Ivan C. Moura, Stéphane Cherif, Hélène Laude, Emmanuel Martin, Lucia Guerri, Cécile Toly, Livine Duban, Anne Devys, Florence Tilloy, Sylvain Latour, Virginie Premel, Gabriella Vera, Olivier Lantz, Emmanuel Treiner, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm U925, équipe avenir, Développement normal et pathologique des lymphocytes et signalisation, Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang [Nantes], Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from INSERM, Action incitative (ACI) 'physiologie integrative,' Agence Nationale pour la Recherche (ANR), and Section Médicale de l'Institut Curie. The development of the 3C10 antibody was funded in part by Innate-Pharma (Marseille, France). OL is supported by la Ligue Contre le Cancer as an 'équipe labellisée.', Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Immunité et cancer (U932), and Autard, Delphine
Subjects: Adoptive cell transfer, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH : Kruppel-Like Transcription Factors, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, MESH: Histocompatibility Antigens Class I, Mice, 0302 clinical medicine, MESH : Child, T-Lymphocyte Subsets, MESH: Child, Cytotoxic T cell, Promyelocytic Leukemia Zinc Finger Protein, MESH: Animals, Biology (General), Child, Mice, Knockout, 0303 health sciences, B-Lymphocytes, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, MESH : Immunity, Mucosal, General Neuroscience, Natural killer T cell, Fetal Blood, MESH : Mice, Transgenic, Cell biology, MESH : Receptors, Antigen, T-Cell, alpha-beta, MESH : Histocompatibility Antigens Class I, MESH: Kruppel-Like Transcription Factors, Antibody, General Agricultural and Biological Sciences, Research Article, Genetically modified mouse, MESH: Mice, Transgenic, QH301-705.5, Immunology, Kruppel-Like Transcription Factors, Mice, Transgenic, Mucosal associated invariant T cell, Thymus Gland, Major histocompatibility complex, General Biochemistry, Genetics and Molecular Biology, MESH : B-Lymphocytes, Minor Histocompatibility Antigens, 03 medical and health sciences, MESH: B-Lymphocytes, MESH : Mice, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, MESH : Thymus Gland, MESH: Fetal Blood, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Immunity, Mucosal, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH : T-Lymphocytes, MESH : Fetal Blood, MESH: Humans, General Immunology and Microbiology, T-cell receptor, Histocompatibility Antigens Class I, MESH : Humans, MESH: Thymus Gland, MESH : Natural Killer T-Cells, MESH : T-Lymphocyte Subsets, Gastrointestinal Tract, MESH: T-Lymphocytes, MESH: Natural Killer T-Cells, MESH: Immunity, Mucosal, biology.protein, Natural Killer T-Cells, MESH : Mice, Knockout, MESH: Gastrointestinal Tract, MESH : Animals, MESH : Gastrointestinal Tract, 030215 immunology
Abstract: Mucosal-associated invariant T (MAIT) cells display two evolutionarily conserved features: an invariant T cell receptor (TCR)α (iTCRα) chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC) molecule, MHC-related molecule 1 (MR1). MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanVα7.2 antibody and MAIT cell-specific iTCRα and TCRβ transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRα and TCRβ transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT) cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%–4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the periphery in a process dependent both upon B cells and the bacterial flora. Thus, their development follows a unique pattern at the crossroad of NKT and γδ T cells., Author Summary White blood cells, or lymphocytes, play an important role in defending the body from infection and disease. T lymphocytes come in many varieties with diverse functions. Mucosal-associated invariant T (MAIT) cells constitute a subset of unconventional T lymphocytes, characterized by their invariant T cell receptor (TCR)α chain and their requirement for the nonpolymorphic class Ib (MHC) molecule, MR1. MAIT cells are extremely abundant in human blood and mucosae. Contrary to mainstream T cells, their development requires B cells and commensal microbial flora. To shed light on the little-understood MAIT cells, we used new tools, including an antibody that we recently developed to detect human MAIT cells, and we were able to show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. We show that thymic selection is MR1 dependent but requires neither B cells nor the commensal flora, which are both necessary for the expansion in the periphery. In contrast with the other evolutionarily conserved invariant subset, the natural killer T (NKT) cells, we found that MAIT cells exit the thymus as “naïve” cells before becoming antigen-experienced memory cells and expanding in number to represent a significant 1%–4% of peripheral T cells in human blood. In mice, we found that MAIT cells remain naïve and do not expand substantially. We conclude that MAIT cell development follows a unique scheme, where, unlike NKT cells, MAIT cell selection and expansion are uncoupled events that are mediated by distinct cell types in different compartments., Mucosal-associated invariant T cells, the most abundant invariant T cell subset in humans, arise via a distinct developmental pathway that represents a hybrid of that seen for NKT and γδ T cells, two other unconventional T cell subsets.
Published: 2009

20. NKT cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner

Author: André Herbelin, Céline Tomkiewicz, Agnès Lehuen, Julien Diana, Thibault Griseri, Anne-Sophie Gautron, Lucie Beaudoin, Matthias von Herrath, Robert Barouki, Marc Dalod, Sylvie Lagaye, Elodie Autrusseau, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Slama, Catherine, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Pharmacologie, toxicologie et signalisation cellulaire (U747), La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Cochin [AP-HP], Physiologie Cellulaire des Regulations Hormonales, Nutritionnelles et Pharmacologiques, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), La Jolla Institute for Allergy and Immunology (LIA), La Jolla Institute for Allergy & Immunology, and Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Signal Transduction, MESH: Spleen, Plasmacytoid dendritic cell, CD8-Positive T-Lymphocytes, Virus Replication, Mice, 0302 clinical medicine, Interferon, Immunology and Allergy, Lymphocytic choriomeningitis virus, MESH: Animals, MESH : Pancreas, MESH: Organ Specificity, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH: Dendritic Cells, hemic and immune systems, MESH : CD8-Positive T-Lymphocytes, MESH: Pancreas, MESH: Receptors, OX40, Acquired immune system, MESH: CD8-Positive T-Lymphocytes, 3. Good health, MESH : Virus Replication, MESH : Diabetes Mellitus, medicine.anatomical_structure, Infectious Diseases, Liver, Organ Specificity, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Lymphocytic choriomeningitis virus, medicine.drug, Signal Transduction, MESH : Spleen, MESH : Lymphocytic Choriomeningitis, MESH: Diabetes Mellitus, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Lymphocytic Choriomeningitis, Immunology, Spleen, OX40 Ligand, Biology, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis, MESH: OX40 Ligand, MESH : Lymphocytic choriomeningitis virus, MESH : Organ Specificity, 03 medical and health sciences, Immune system, MESH : Mice, medicine, Diabetes Mellitus, Animals, MESH : OX40 Ligand, MESH: Mice, Pancreas, 030304 developmental biology, MESH : Signal Transduction, MESH: Virus Replication, MESH : Liver, Dendritic Cells, Receptors, OX40, medicine.disease, MESH : Natural Killer T-Cells, Viral replication, MESH: Natural Killer T-Cells, CELLIMMUNO, MESH : Dendritic Cells, Natural Killer T-Cells, MESH : Animals, MESH : Receptors, OX40, CD8, 030215 immunology, MESH: Liver
Abstract: International audience; Invariant natural killer T (iNKT) cells promote immune responses to various pathogens, but exactly how iNKT cells control antiviral responses is unclear. Here, we showed that iNKT cells induced tissue-specific antiviral effects in mice infected by lymphocytic choriomeningitis virus (LCMV). Indeed, iNKT cells inhibited viral replication in the pancreas and liver but not in the spleen. In the pancreas, iNKT cells expressed the OX40 molecule and promoted type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) through OX40-OX40 ligand interaction. Subsequently, this iNKT cell-pDC cooperation attenuated the antiviral adaptive immune response in the pancreas but not in the spleen. The dampening of pancreatic anti-LCMV CD8(+) T cell response prevented tissue damage in transgenic mice expressing LCMV protein in islet beta cells. Thus, this study identifies pDCs as an essential partner of iNKT cells for mounting an efficient, nondeleterious antiviral response in peripheral tissue.
Published: 2007

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20 results on '"MESH: Natural Killer T-Cells"'

1. SLAM-associated protein favors the development of iNKT2 over iNKT17 cells

2. Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation

3. Fine tuning by human CD1e of lipid-specific immune responses

4. TCR-inducible PLZF transcription factor required for innate phenotype of a subset of γδ T cells with restricted TCR diversity

5. Human CD4+invariant NKT cells are involved in antibacterial immunity againstBrucella suisthrough CD1d-dependent but CD4-independent mechanisms

6. Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin

7. Invariant NKT cells regulate the CD8 T cell response during Theiler's virus infection

8. TRAIL but not FasL and TNFα, regulates IL-33 expression in murine hepatocytes during acute hepatitis

9. Dok-1 overexpression promotes development of γδ natural killer T cells

10. Key role for respiratory CD103(+) dendritic cells, IFN-γ, and IL-17 in protection against Streptococcus pneumoniae infection in response to α-galactosylceramide

11. Identification of invariant natural killer T cells in porcine peripheral blood

12. NKT cells are required to induce high IL-33 expression in hepatocytes during ConA-induced acute hepatitis

13. Invariant natural killer T-cell-deficient mice display increased CCl₄ -induced hepatitis associated with CXCL1 over-expression and neutrophil infiltration

14. Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay

15. Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of peripheral lymph node NK1.1- invariant NKT cells to bacteria

16. Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions

17. iNKT cell development is orchestrated by different branches of TGF-beta signaling

18. The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-gamma production

19. Stepwise development of MAIT cells in mouse and human

20. NKT cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner

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20 results on '"MESH: Natural Killer T-Cells"'

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