| Autor: |
Alejandro Carrillo-Jimenez, Özgen Deniz, Maria Victoria Niklison-Chirou, Rocio Ruiz, Karina Bezerra-Salomão, Vassilis Stratoulias, Rachel Amouroux, Ping Kei Yip, Anna Vilalta, Mathilde Cheray, Alexander Michael Scott-Egerton, Eloy Rivas, Khadija Tayara, Irene García-Domínguez, Juan Garcia-Revilla, Juan Carlos Fernandez-Martin, Ana Maria Espinosa-Oliva, Xianli Shen, Peter St George-Hyslop, Guy Charles Brown, Petra Hajkova, Bertrand Joseph, Jose Luis Venero, Miguel Ramos Branco, Miguel Angel Burguillos |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 29, Iss 3, Pp 697-713.e8 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.09.013 |
| 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: |
Directory of Open Access Journals |
| Externí odkaz: |
|
