TET2 regulates the neuroinflammatory response in microglia
| Autor: | Ana M. Espinosa-Oliva, José L. Venero, Juan Carlos Fernandez-Martin, Peter St George-Hyslop, Alexander Michael Scott-Egerton, Özgen Deniz, Guy C. Brown, Vassilis Stratoulias, Khadija Tayara, Irene García-Domínguez, Karina Bezerra-Salomão, Petra Hajkova, Mathilde Cheray, Alejandro Carrillo-Jimenez, Maria Victoria Niklison-Chirou, Bertrand Joseph, Miguel Angel Burguillos, Rocío Ruiz, Ping K. Yip, Juan García-Revilla, Anna Vilalta, Eloy Rivas, Rachel Amouroux, Miguel R. Branco, Xianli Shen |
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| Přispěvatelé: | St George-Hyslop, Peter [0000-0003-0796-7209], Brown, Guy [0000-0002-3610-1730], Apollo - University of Cambridge Repository, Commission of the European Communities, Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male Transcription Genetic microglia Nitric Oxide Synthase Type II Stimulation 0601 Biochemistry and Cell Biology neuroinflammation Mice 0302 clinical medicine RNA Small Interfering lcsh:QH301-705.5 Epigenomics Mice Knockout 0303 health sciences Microglia Neurodegeneration Brain TLR-4 Cell biology DNA-Binding Proteins Enhancer Elements Genetic medicine.anatomical_structure RNA Interference Amyloid Cell type Biology General Biochemistry Genetics and Molecular Biology Dioxygenases Proinflammatory cytokine 03 medical and health sciences Immune system Alzheimer Disease Proto-Oncogene Proteins medicine Animals Humans Epigenetics Neuroinflammation 030304 developmental biology TET2 epigenetics Interleukin-6 Transcription Factor RelA NFKB1 medicine.disease Rats Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) metabolism 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports Cell Reports, Vol 29, Iss 3, Pp 697-713.e8 (2019) 713.e8 idUS. Depósito de Investigación de la Universidad de Sevilla instname |
| Popis: | Summary: Epigenomic mechanisms regulate distinct aspects of the inflammatory response in immune cells. Despite the central role for microglia in neuroinflammation and neurodegeneration, little is known about their epigenomic regulation of the inflammatory response. Here, we show that Ten-eleven translocation 2 (TET2) methylcytosine dioxygenase expression is increased in microglia upon stimulation with various inflammogens through a NF-κB-dependent pathway. We found that TET2 regulates early gene transcriptional changes, leading to early metabolic alterations, as well as a later inflammatory response independently of its enzymatic activity. We further show that TET2 regulates the proinflammatory response in microglia of mice intraperitoneally injected with LPS. We observed that microglia associated with amyloid β plaques expressed TET2 in brain tissue from individuals with Alzheimer’s disease (AD) and in 5xFAD mice. Collectively, our findings show that TET2 plays an important role in the microglial inflammatory response and suggest TET2 as a potential target to combat neurodegenerative brain disorders. : Microglia play a key role in neuroinflammation and neurodegeneration in different neurodegenerative diseases, but little is known about the epigenetic modifying enzymes regulating their inflammatory response. Carrillo-Jimenez et al. identify TET2 as a major regulator of the microglia proinflammatory response and suggest that, by targeting this protein, microglial activation could be impaired. Keywords: microglia, epigenetics, TET2, metabolism, TLR-4, neuroinflammation |
| Databáze: | OpenAIRE |
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