The Nuclear Receptor Nr4a1 Acts as a Microglia Rheostat and Serves as a Therapeutic Target in Autoimmune-Driven Central Nervous System Inflammation

التفاصيل البيبلوغرافية
العنوان: The Nuclear Receptor Nr4a1 Acts as a Microglia Rheostat and Serves as a Therapeutic Target in Autoimmune-Driven Central Nervous System Inflammation
المؤلفون: Georg Schett, Gerhard Krönke, Tobias Rothe, Beate Winner, Daniel Metzger, Francesc Pérez-Brangulí, Hiroshi Ichinose, Maria Faas, Natacha Ipseiz, Stefanie C. Lang
المساهمون: University Hospital Erlangen = Uniklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Tokyo Institute of Technology [Tokyo] (TITECH), univOAK, Archive ouverte
المصدر: The Journal of Immunology
Journal of Immunology
Journal of Immunology, 2017, 198 (10), pp.3878-3885. ⟨10.4049/jimmunol.1600638⟩
سنة النشر: 2017
مصطلحات موضوعية: Central Nervous System, 0301 basic medicine, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, Immunology, Central nervous system, Regulator, Inflammation, Biology, Nitric Oxide, Article, Mice, 03 medical and health sciences, Adenosine Triphosphate, 0302 clinical medicine, Central Nervous System Diseases, Nuclear Receptor Subfamily 4, Group A, Member 1, medicine, Animals, Humans, Immunology and Allergy, Cells, Cultured, Microglia, Multiple sclerosis, Experimental autoimmune encephalomyelitis, Neurodegenerative Diseases, Macrophage Activation, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Cytokine, medicine.anatomical_structure, Gene Expression Regulation, nervous system, Nuclear receptor, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, medicine.symptom, Neuroscience, 030217 neurology & neurosurgery
الوصف: Microglia cells fulfill key homeostatic functions and essentially contribute to host defense within the CNS. Altered activation of microglia, in turn, has been implicated in neuroinflammatory and neurodegenerative diseases. In this study, we identify the nuclear receptor (NR) Nr4a1 as key rheostat controlling the activation threshold and polarization of microglia. In steady-state microglia, ubiquitous neuronal-derived stress signals such as ATP induced expression of this NR, which contributed to the maintenance of a resting and noninflammatory microglia phenotype. Global and microglia-specific deletion of Nr4a1 triggered the spontaneous and overwhelming activation of microglia and resulted in increased cytokine and NO production as well as in an accelerated and exacerbated form of experimental autoimmune encephalomyelitis. Ligand-induced activation of Nr4a1 accordingly ameliorated the course of this disease. Our current data thus identify Nr4a1 as regulator of microglia activation and potentially new target for the treatment of inflammatory CNS diseases such as multiple sclerosis.
تدمد: 0022-1767
1550-6606
DOI: 10.4049/jimmunol.1600638
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8313c6ff487af18beedb8f0a0aaa0668
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....8313c6ff487af18beedb8f0a0aaa0668
قاعدة البيانات: OpenAIRE
الوصف
تدمد:00221767
15506606
DOI:10.4049/jimmunol.1600638