An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes
| العنوان: | An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes |
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| المؤلفون: | Sandrine Levet, Jacques Portoukalian, Julie Dimier, Thomas Piofczyk, Matthieu Normand, Kevin Réant, Hervé Perron, Nelly Queruel, Raphaële Germi, Julie Joanou, Julie Medina, Jean-Louis Touraine, Marine Seffals, Amandine Demolder |
| المساهمون: | Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Normandie Université (NU), H2P2 - Histo Pathologie Hight Precision (H2P2), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherches du Service de Santé des Armées (CRSSA), Service de Santé des Armées, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Department of Plant Developmental Biology, Max Planck Institute for Plant Breeding Research (MPIPZ), Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), N/A, Geneuro Innovation, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES) |
| المصدر: | JCI Insight JCI Insight, American Society for Clinical Investigation, 2017, 2 (17), ⟨10.1172/jci.insight.94387⟩ JCI Insight, 2017, 2 (17), ⟨10.1172/jci.insight.94387⟩ |
| بيانات النشر: | HAL CCSD, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, endocrine system, endocrine system diseases, medicine.medical_treatment, viruses, Mice, Transgenic, Autoimmunity, Biology, medicine.disease_cause, Antiviral Agents, Peripheral blood mononuclear cell, Cohort Studies, Pathogenesis, Insulin Antagonists, Islets of Langerhans, Mice, 03 medical and health sciences, Immune system, Endocrinology, Viral Envelope Proteins, medicine, Animals, Humans, Insulin, Macrophage, Gene, Innate immunity, Innate immune system, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Endogenous Retroviruses, Diabetes, Beta cells, General Medicine, Molecular biology, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Diabetes Mellitus, Type 1, 030104 developmental biology, Hyperglycemia, Immunology, embryonic structures, RNA, Viral, Female, Research Article |
| الوصف: | International audience; Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W-Env) has been involved in multiple sclerosis pathogenesis. Investigations to detect HERV-W-Env in a few other autoimmune diseases were negative, except in type-1 diabetes (T1D). In patients suffering from T1D, HERV-W-Env protein was detected in 70% of sera, and its corresponding RNA was detected in 57% of peripheral blood mononuclear cells. While studies on human Langerhans islets evidenced the inhibition of insulin secretion by HERV-W-Env, this endogenous protein was found to be expressed by acinar cells in 75% of human T1D pancreata. An extensive immunohistological analysis further revealed a significant correlation between HERV-W-Env expression and macrophage infiltrates in the exocrine part of human pancreata. Such findings were corroborated by in vivo studies on transgenic mice expressing HERV-W-env gene, which displayed hyperglycemia and decreased levels of insulin, along with immune cell infiltrates in their pancreas. Altogether, these results strongly suggest an involvement of HERV-W-Env in T1D pathogenesis. They also provide potentially novel therapeutic perspectives, since unveiling a pathogenic target in T1D. |
| اللغة: | English |
| تدمد: | 2379-3708 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa746a24fb768362edc718f85c7224e8 https://hal.archives-ouvertes.fr/hal-02059891 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fa746a24fb768362edc718f85c7224e8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23793708 |
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