دورية أكاديمية
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: | Levet, Sandrine, Medina, Julie, Joanou, Julie, Demolder, Amandine, Queruel, Nelly, Réant, Kevin, Normand, Matthieu, Seffals, Marine, Dimier, Julie, Germi, Raphaële, Piofczyk, Thomas, Portoukalian, Jacques, Touraine, Jean-Louis, Perron, Hervé |
| المساهمون: | Biologie du Cancer et de l'Infection (BCI ), 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), 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 (UR)-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 2016-2019 (UGA 2016-2019 ), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes 2016-2019 (UGA 2016-2019 )-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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 |
| المصدر: | ISSN: 2379-3708 ; JCI Insight ; https://hal.science/hal-02059891Test ; JCI Insight, 2017, 2 (17), ⟨10.1172/jci.insight.94387⟩. |
| بيانات النشر: | HAL CCSD American Society for Clinical Investigation |
| سنة النشر: | 2017 |
| المجموعة: | Normandie Université: HAL |
| مصطلحات موضوعية: | Autoimmunity, Beta cells, Diabetes, Endocrinology, Innate immunity, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] |
| 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/28878130; hal-02059891; https://hal.science/hal-02059891Test; PUBMED: 28878130; PUBMEDCENTRAL: PMC5621895 |
| DOI: | 10.1172/jci.insight.94387 |
| الإتاحة: | https://doi.org/10.1172/jci.insight.94387Test https://hal.science/hal-02059891Test |
| رقم الانضمام: | edsbas.7121D134 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1172/jci.insight.94387 |
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