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The Nuclear Receptor Nr4a1 Acts as a Microglia Rheostat and Serves as a Therapeutic Target in Autoimmune-Driven Central Nervous System Inflammation
The Nuclear Receptor Nr4a1 Acts as a Microglia Rheostat and Serves as a Therapeutic Target in Autoimmune-Driven Central Nervous System Inflammation
- Source :
- The Journal of Immunology, Journal of Immunology, Journal of Immunology, 2017, 198 (10), pp.3878-3885. ⟨10.4049/jimmunol.1600638⟩
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 00221767 and 15506606
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....8313c6ff487af18beedb8f0a0aaa0668
- Full Text :
- https://doi.org/10.4049/jimmunol.1600638