Search

Your search keyword '"MESH : Mice, Mutant Strains"' showing total 6 results
Start Over Descriptor "MESH : Mice, Mutant Strains"
6 results on '"MESH : Mice, Mutant Strains"'

1. Th2 Lymphoproliferative Disorder of Lat Y136F Mutant Mice Unfolds Independently of TCR-MHC Engagement and Is Insensitive to the Action of Foxp3+ Regulatory T Cells

Author

Céline Genton, Adrien Kissenpfennig, Michael Mingueneau, Hans Acha-Orbea, Marie Malissen, Sylvie Richelme, Ying Wang, Pierre Perrin, Stéphane Chevrier, Bruno Lucas, James P. DiSanto, Bernard Malissen, 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), Department of Biochemistry [Lausanne], Université de Lausanne (UNIL), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Cytokines et Développement Lymphoïde, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne = University of Lausanne (UNIL), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), Department of Biochemistry, Université de Lausanne ( UNIL ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
Adoptive cell transfer, MESH: Mice, Mutant Strains, MESH: Antigens, CD4, MESH : Green Fluorescent Proteins, T-Lymphocytes, Regulatory, MESH : Receptors, Antigen, T-Cell, MESH : T-Lymphocytes, Regulatory, Mice, MESH: Lymphoproliferative Disorders, 0302 clinical medicine, MESH: Autoimmune Diseases, MESH : Cell Proliferation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Autoantibodies, Immunology and Allergy, MESH: Animals, MESH : Adaptor Proteins, Signal Transducing, 0303 health sciences, MESH : Lymphoproliferative Disorders, biology, FOXP3, Forkhead Transcription Factors, MESH: Receptors, Antigen, T-Cell, 3. Good health, MESH : Forkhead Transcription Factors, MESH : Histocompatibility Antigens Class II, CD4 Antigens, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Membrane Proteins, MESH : Interleukin-7, Green Fluorescent Proteins, Immunology, Receptors, Antigen, T-Cell, Linker for Activation of T cells, Major histocompatibility complex, MESH: Phosphoproteins, Autoimmune Diseases, 03 medical and health sciences, MESH : Autoimmune Diseases, Th2 Cells, MESH: Green Fluorescent Proteins, Antigen, MESH: Forkhead Transcription Factors, MESH: Th2 Cells, MESH : Autoantibodies, MESH: Cell Proliferation, MESH : Mice, MHC class I, Animals, MESH: Mice, Adaptor Proteins, Signal Transducing, Autoantibodies, Cell Proliferation, MESH: Adaptor Proteins, Signal Transducing, 030304 developmental biology, Interleukin-7, MESH: T-Lymphocytes, Regulatory, T-cell receptor, Histocompatibility Antigens Class II, Autoantibody, Membrane Proteins, Phosphoproteins, Molecular biology, Lymphoproliferative Disorders, Mice, Mutant Strains, MESH: Interleukin-7, MESH : Th2 Cells, MESH : Mice, Mutant Strains, MESH : Membrane Proteins, MESH: Histocompatibility Antigens Class II, biology.protein, MESH : Antigens, CD4, MESH : Animals, MESH : Phosphoproteins, 030215 immunology
Abstract

Mutant mice where tyrosine 136 of linker for activation of T cells (LAT) was replaced with a phenylalanine (LatY136F mice) develop a fast-onset lymphoproliferative disorder involving polyclonal CD4 T cells that produce massive amounts of Th2 cytokines and trigger severe inflammation and autoantibodies. We analyzed whether the LatY136F pathology constitutes a bona fide autoimmune disorder dependent on TCR specificity. Using adoptive transfer experiments, we demonstrated that the expansion and uncontrolled Th2-effector function of LatY136F CD4 cells are not triggered by an MHC class II-driven, autoreactive process. Using Foxp3EGFP reporter mice, we further showed that nonfunctional Foxp3+ regulatory T cells are present in LatY136F mice and that pathogenic LatY136F CD4 T cells were capable of escaping the control of infused wild-type Foxp3+ regulatory T cells. These results argue against a scenario where the LatY136F pathology is primarily due to a lack of functional Foxp3+ regulatory T cells and suggest that a defect intrinsic to LatY136F CD4 T cells leads to a state of TCR-independent hyperactivity. This abnormal status confers LatY136F CD4 T cells with the ability to trigger the production of Abs and of autoantibodies in a TCR-independent, quasi-mitogenic fashion. Therefore, despite the presence of autoantibodies causative of severe systemic disease, the pathological conditions observed in LatY136F mice unfold in an Ag-independent manner and thus do not qualify as a genuine autoimmune disorder.

Published
2008
Full Text
View/download PDF

2. Stromal cell networks regulate thymocyte migration and dendritic cell behavior in the thymus

Author

Jonathan A. Nowak, Marc Bajénoff, Mathieu Fallet, Stephanie L. Sanos, 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 ), 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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
Chemokine, MESH: Mice, Mutant Strains, MESH : Antigens, Cell Communication, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, MESH : Radiation Chimera, Mice, 0302 clinical medicine, Cell Movement, T-Lymphocyte Subsets, Immunology and Allergy, MESH : Cell Movement, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Cell Movement, Mice, Knockout, 0303 health sciences, MESH: Dendritic Cells, Cell biology, Thymocyte, medicine.anatomical_structure, Radiation Chimera, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Antigens, Thymocyte migration, Stromal cell, MESH : Cell Communication, MESH: Radiation Chimera, T cell, Immunology, Thymus Gland, MESH : Mice, Inbred C57BL, Biology, 03 medical and health sciences, MESH : Microscopy, Fluorescence, Multiphoton, MESH: Mice, Inbred C57BL, MESH: Cell Communication, MESH : Mice, medicine, Animals, MESH : Thymus Gland, Progenitor cell, Antigens, MESH: Mice, 030304 developmental biology, Dendritic cell, Dendritic Cells, MESH: Thymus Gland, Mice, Mutant Strains, MESH : T-Lymphocyte Subsets, Mice, Inbred C57BL, MESH : Mice, Mutant Strains, Microscopy, Fluorescence, Multiphoton, MESH : Stromal Cells, MESH : Dendritic Cells, T cell migration, biology.protein, MESH: Microscopy, Fluorescence, Multiphoton, MESH : Mice, Knockout, MESH : Animals, Stromal Cells, MESH: Stromal Cells, 030215 immunology
Abstract

After entry into thymus, T cell progenitors migrate in the cortex and the medulla while completing their education. Recent reports have documented the dynamic and tortuous behavior of thymocytes. However, other than chemokines and/or segregated thymic substrates, the factors contributing to the dynamic patterns of thymocyte movement are poorly characterized. By combining confocal and dynamic two-photon microscopy, we demonstrate that thymocytes continuously migrate on thymic stromal cell networks. In addition to constituting “roads” for thymocytes, we observed that these networks also provide a scaffold on which dendritic cells attach themselves. These results highlight the central role of stromal microanatomy in orchestrating the multiple cellular interactions necessary for T cell migration/development within the thymus.

Published
2011
Full Text
View/download PDF

3. Evidence of a dosage effect and a physiological endplate acetylcholinesterase deficiency in the first mouse models mimicking Schwartz-Jampel syndrome neuromyotonia

Author

Morgane Stum, Arnaud Ferry, Frédédrique Rene, Christophe Marcel, Andoni Echaniz-Laguna, Véronique Bernard, Claire-Sophie Davoine, Bertrand Fontaine, Eric Krejci, Sophie Nicole, Alban Vignaud, Marie Bangratz, Emmanuelle Girard, Jordi Molgó, Marc Herbin, Affections de la Myeline et des Canaux Ioniques Musculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Biologie des Jonctions Neuromusculaires Normales et Pathologiques (U686), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Mécanismes adaptatifs : des organismes aux communautés (MAOAC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Groupe Myologie, Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Neurologie, Hôpital Civil de Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Muséum national d'Histoire naturelle (MNHN)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Laboratoire de neurobiologie cellulaire et moléculaire ( NBCM ), Centre National de la Recherche Scientifique ( CNRS ), Institut de Neurobiologie Alfred Fessard ( INAF ), Biologie des Jonctions Neuromusculaires Normales et Pathologiques ( U686 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Mécanismes adaptatifs : des organismes aux communautés ( MAOAC ), Muséum National d'Histoire Naturelle ( MNHN ) -Collège de France ( CdF ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]

Subjects
Male, Neuromyotonia, MESH: Mice, Mutant Strains, MESH: Muscle Contraction, Gene Dosage, medicine.disease_cause, MESH: Gene Dosage, MESH: Motor Endplate, chemistry.chemical_compound, Mice, 0302 clinical medicine, Missense mutation, MESH : Female, MESH : Gene Dosage, MESH: Animals, Genetics (clinical), 0303 health sciences, Mutation, biology, General Medicine, Acetylcholinesterase, MESH : Mice, Transgenic, MESH : Phenotype, medicine.anatomical_structure, Phenotype, MESH : Electromyography, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Heparan Sulfate Proteoglycans, Muscle Contraction, medicine.medical_specialty, MESH : Isaacs Syndrome, MESH: Mice, Transgenic, MESH : Male, Schwartz–Jampel syndrome, Mutation, Missense, Mice, Transgenic, MESH : Mice, Inbred C57BL, Perlecan, Osteochondrodysplasias, MESH: Phenotype, Motor Endplate, Neuromuscular junction, MESH : Acetylcholinesterase, MESH: Electromyography, 03 medical and health sciences, In vivo, MESH: Mice, Inbred C57BL, Internal medicine, MESH : Mice, Genetics, medicine, Animals, Humans, MESH: Isaacs Syndrome, Molecular Biology, MESH: Mice, Alleles, 030304 developmental biology, MESH : Osteochondrodysplasias, MESH: Mutation, Missense, MESH: Humans, Electromyography, MESH: Alleles, MESH : Humans, MESH : Motor Endplate, MESH: Acetylcholinesterase, medicine.disease, MESH: Osteochondrodysplasias, MESH : Disease Models, Animal, Mice, Mutant Strains, MESH: Male, MESH : Mice, Mutant Strains, Mice, Inbred C57BL, Disease Models, Animal, stomatognathic diseases, Endocrinology, chemistry, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], biology.protein, MESH: Heparan Sulfate Proteoglycans, MESH : Muscle Contraction, MESH : Animals, Isaacs Syndrome, MESH: Disease Models, Animal, MESH : Alleles, MESH: Female, MESH : Mutation, Missense, 030217 neurology & neurosurgery, Heparan Sulfate Proteoglycans
Abstract

International audience; Schwartz-Jampel syndrome (SJS) is a recessive neuromyotonia with chondrodysplasia. It results from hypomorphic mutations of the gene encoding perlecan, leading to a decrease in the levels of this heparan sulphate proteoglycan in basement membranes (BMs). It has been suggested that SJS neuromyotonia may result from endplate acetylcholinesterase (AChE) deficiency, but this hypothesis has never been investigated in vivo due to the lack of an animal model for neuromyotonia. We used homologous recombination to generate a knock-in mouse strain with one missense substitution, corresponding to a human familial SJS mutation (p.C1532Y), in the perlecan gene. We derived two lines, one with the p.C1532Y substitution alone and one with p.C1532Y and the selectable marker Neo, to down-regulate perlecan gene activity and to test for a dosage effect of perlecan in mammals. These two lines mimicked SJS neuromyotonia with spontaneous activity on electromyogramm (EMG). An inverse correlation between disease severity and perlecan secretion in the BMs was observed at the macroscopic and microscopic levels, consistent with a dosage effect. Endplate AChE levels were low in both lines, due to synaptic perlecan deficiency rather than major myofibre or neuromuscular junction disorganization. Studies of muscle contractile properties showed muscle fatigability at low frequencies of nerve stimulation and suggested that partial endplate AChE deficiency might contribute to SJS muscle stiffness by potentiating muscle force. However, physiological endplate AChE deficiency was not associated with spontaneous activity at rest on EMG in the diaphragm, suggesting that additional changes are required to generate such activity characteristic of SJS.

Published
2008
Full Text
View/download PDF

4. Fibroblastic reticular cells guide T lymphocyte entry into and migration within the splenic T cell zone

Author

Marc Bajénoff, Ronald N. Germain, Nicolas Glaichenhaus, Lymphocyte Biology Section ( NIAID ), National Institutes of Health, Immunologie des Maladies Infectieuses Allergiques et Autoimmunes, Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lymphocyte Biology Section (NIAID), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Pathology, MESH: Spleen, MESH: Mice, Mutant Strains, Lymphocyte, MESH: Chemotaxis, Leukocyte, MESH : Arterioles, MESH: T-Lymphocyte Subsets, MESH : Radiation Chimera, 0302 clinical medicine, Reticular cell, Immunology and Allergy, Cytotoxic T cell, MESH: Microscopy, Confocal, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Chemokine CCL21, 0303 health sciences, MESH : Adoptive Transfer, MESH : Chemotaxis, Leukocyte, Marginal zone, Cell biology, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Lymph, MESH: B-Lymphocyte Subsets, MESH : Spleen, medicine.medical_specialty, MESH: Radiation Chimera, T cell, Immunology, MESH : Mice, Inbred C57BL, Biology, 03 medical and health sciences, MESH: Arterioles, MESH: Mice, Inbred C57BL, MESH : Fibroblasts, MESH : Mice, medicine, MESH : Microscopy, Confocal, MESH: Mice, 030304 developmental biology, MESH: Chemokine CCL21, T lymphocyte, MESH : T-Lymphocyte Subsets, MESH : Mice, Mutant Strains, MESH: Adoptive Transfer, MESH: Fibroblasts, MESH : Stromal Cells, MESH : Animals, MESH: Stromal Cells, Periarteriolar lymphoid sheaths, 030215 immunology, MESH : B-Lymphocyte Subsets
Abstract

Although a great deal is known about T cell entry into lymph nodes, much less is understood about how T lymphocytes access the splenic white pulp (WP). We show in this study that, as recently described for lymph nodes, fibroblastic reticular cells (FRCs) form a network in the T cell zone (periarteriolar lymphoid sheath, PALS) of the WP on which T lymphocytes migrate. This network connects the PALS to the marginal zone (MZ), which is the initial site of lymphocyte entry from the blood. T cells do not enter the WP at random locations but instead traffic to that site using the FRC-rich MZ bridging channels (MZBCs). These data reveal that FRCs form a substrate for T cells in the spleen, guiding these lymphocytes from their site of entry in the MZ into the PALS, within which they continue to move on the same network.

Published
2008

5. The Pro-Th1 cytokine IL-12 enhances IL-4 production by invariant NKT cells: relevance for T cell-mediated hepatitis

Author

Diane Damotte, Luiza M Araujo, André Herbelin, Michel Dy, Emilie Philadelphe, Elke Schneider, Michel Samson, Séverine Diem, Jordan Denizeau, Ren Zhu, Aude Aumeunier, Pierre Gourdy, 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), Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Détoxication et réparation tissulaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hormones, facteurs de croissance et physiopathologie vasculaire, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-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), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR 31 Louis Bugnard ( IFR 31 ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Samson, Michel, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Interleukin-12, MESH: Mice, Mutant Strains, MESH : Cytokines, MESH: T-Lymphocyte Subsets, Hepatitis, Animal, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Concanavalin A, MESH : Th1 Cells, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Interleukin-12 Receptor beta 1 Subunit, MESH : Concanavalin A, NOD mice, 0303 health sciences, education.field_of_study, MESH: Cytokines, MESH: Hepatitis, Animal, Natural killer T cell, Interleukin-12, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, MESH : Interleukin-12 Receptor beta 1 Subunit, Interleukin 12, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Killer Cells, Natural, MESH: Killer Cells, Natural, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Immunology, Population, MESH: Concanavalin A, Biology, MESH : Interleukin-4, 03 medical and health sciences, Immune system, MESH : Mice, Interleukin-12 Receptor beta 1 Subunit, medicine, MESH : Interleukin-12, Animals, Secretion, education, MESH: Mice, Interleukin 4, 030304 developmental biology, Th1 Cells, MESH: Interleukin-4, MESH : Disease Models, Animal, Mice, Mutant Strains, MESH : T-Lymphocyte Subsets, MESH : Mice, Mutant Strains, Disease Models, Animal, MESH: Th1 Cells, Interleukin-4, MESH : Animals, MESH: Disease Models, Animal, MESH : Hepatitis, Animal, 030215 immunology
Abstract

IL-12 is essential for invariant NKT (iNKT) cells because it can maintain a functionally active population and promote a cytokine profile that is assumed to be mainly of the pro-Th1 type. We used the murine concanavalin A (Con A)-induced hepatitis model, in which iNKT cells, IL-12, IL-4, and IFN-γ are equally requisite, to reevaluate this issue. We demonstrate that IL-12 interacts directly with iNKT cells, contributes to their recruitment to the liver, and enhances their IL-4 production, which is essential for disease onset. IL-12-deficient mice were less susceptible to experimental hepatitis and their iNKT cells produced less IL-4 than their wild-type counterpart. A normal response could be restored by IL-12 injection, revealing its importance as endogenous mediator. In accordance with this observation, we found that iNKT cells expressed the IL-12R constitutively, in contrast to conventional T cells. Furthermore, the physiological relevance of our data is supported by the lower susceptibility to disease induction of NOD mice, known for their inherent functional and numerical abnormalities of iNKT cells associated with decreased iNKT cell-derived IL-4 production and low IL-12 secretion. Taken together, our findings provide the first evidence that IL-12 can enhance the immune response through increased IL-4 production by iNKT cells, underscoring once more the functional plasticity of this subset.

Published
2007

6. Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine(2B) receptors in mice

Author

Jean-Marie Launay, Katell Peoc'h, Juan Miguel Esteve, Philippe Hervé, Claire Tournois, Luc Maroteaux, Jacques Callebert, Ludovic Drouet, Service de Biochimie et de Biologie moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Faculté de Pharmacie, Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Faculté de Pharmacie-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Faculté de Pharmacie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Faculté de Pharmacie-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, MESH : Hypertension, Pulmonary, MESH: Mice, Mutant Strains, MESH : Serotonin, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Anoxia, Stimulation, 030204 cardiovascular system & hematology, Pharmacology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Mice, 0302 clinical medicine, MESH : Receptor, Serotonin, 5-HT2B, Receptor, Serotonin, 5-HT2B, MESH : Female, MESH: Animals, Hypoxia, Receptor, Lung, Serotonin transporter, 0303 health sciences, biology, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Pulmonary Artery, 3. Good health, MESH: Serotonin 5-HT2 Receptor Antagonists, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Serotonin 5-HT2 Receptor Antagonists, Molecular Medicine, Female, medicine.symptom, Agonist, Serotonin, medicine.medical_specialty, Serotonin uptake, MESH : Anoxia, medicine.drug_class, Hypertension, Pulmonary, MESH : Lung, MESH : Male, MESH: Pulmonary Artery, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Pulmonary Artery, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, MESH : Mice, medicine, Animals, MESH: Lung, MESH: Mice, 030304 developmental biology, MESH: Hypertension, Pulmonary, MESH: Receptor, Serotonin, 5-HT2B, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [ SDV.GEN.GA ] Life Sciences [q-bio]/Genetics/Animal genetics, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Hypoxia (medical), medicine.disease, Pulmonary hypertension, Mice, Mutant Strains, MESH: Male, MESH : Mice, Mutant Strains, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Endocrinology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Serotonin, MESH : Animals, MESH : Serotonin 5-HT2 Receptor Antagonists, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract

International audience; A correlation between high plasma serotonin levels and total pulmonary resistance was reported in more than 80% of pulmonary hypertensive patients. When submitted to chronic hypoxia (10% O(2) for more than 3 weeks), wild-type mice develop lung vascular remodeling and pulmonary hypertension. We previously reported that, in contrast, the development of these hypoxia-dependent alterations is totally abolished in mice with permanent (genetic) or transient (pharmacologic) inactivation of the serotonin 5-hydroxytryptamine (5-HT)(2B) receptor. In the present study, we asked whether 5-HT(2B) receptors could be involved in the control of plasma serotonin levels. Further investigating the chronic hypoxic mouse model of pulmonary hypertension, we first show that in wild-type mice, plasma serotonin levels and 5-HT(2B) receptors expression were significantly increased after chronic exposure to hypoxia. This increase appeared before significant changes in remodeling factors could be detected and persisted when the pathology was established. Conversely, in mice with either genetically or pharmacologically inactive 5-HT(2B) receptors, plasma serotonin levels were not modified by chronic hypoxia. We then confirmed that 5-HT(2B) receptors can control plasma serotonin levels by providing in vivo evidence that an acute agonist stimulation of 5-HT(2B) receptor triggers a transient increase in plasma serotonin that is serotonin transporter dependent and blocked by 5-HT(2B) receptor-selective antagonist or genetic ablation. Our data support the notion that a 5-HT(2B) receptor-dependent regulation of serotonin uptake is implicated in the control of plasma serotonin levels.

Published
2006
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results