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

Rothe T, Ipseiz N, Faas M, Lang S, Perez-Branguli F, Metzger D, Ichinose H, Winner B, Schett G, Krönke G (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Journal of Immunology American Association of Immunologists

DOI: 10.4049/jimmunol.1600638

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.

Authors with CRIS profile

Maria Faas Professur für Immunologie Stefanie Lang Department of Medicine 3 – Rheumatology and Immunology Beate Winner Professur für Stammzell-Modelle seltener neuraler Erkrankungen Georg Schett Lehrstuhl für Innere Medizin III Gerhard Krönke Professur für Translationale Immunologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Tokyo Institute of Technology JP Japan (JP) Université de Strasbourg (UDS) FR France (FR)

How to cite

APA:

Rothe, T., Ipseiz, N., Faas, M., Lang, S., Perez-Branguli, F., Metzger, D.,... Krönke, G. (2017). The Nuclear Receptor Nr4a1 Acts as a Microglia Rheostat and Serves as a Therapeutic Target in Autoimmune-Driven Central Nervous System Inflammation. Journal of Immunology. https://dx.doi.org/10.4049/jimmunol.1600638

MLA:

Rothe, Tobias, et al. "The Nuclear Receptor Nr4a1 Acts as a Microglia Rheostat and Serves as a Therapeutic Target in Autoimmune-Driven Central Nervous System Inflammation." Journal of Immunology (2017).

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