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Title TET2 Regulates the Neuroinflammatory Response in Microglia
Authors Carrillo-Jimenez, Alejandro , Deniz, Ozgen , Niklison-Chirou, Maria Victoria , Ruiz, Rocio , Bezerra-Salomao, Karina , Stratoulias, Vassilis , Amouroux, Rachel , Yip, Ping Kei , Vilalta, Anna , Cheray, Mathilde , Scott-Egerton, Alexander Michael , Rivas, Eloy , Tayara, Khadija , GARCÍA DOMÍNGUEZ, IRENE, Garcia-Revilla, Juan , Carlos Fernandez-Martin, Juan , Maria Espinosa-Oliva, Ana , Shen, Xianli , St George-Hyslop, Peter , Brown, Guy Charles , Hajkova, Petra , Joseph, Bertrand , Luis Venero, Jose , Branco, Miguel Ramos , Angel Burguillos, Miguel
External publication Si
Means Cell Reports
Scope Article
Nature Científica
JCR Quartile 1
SJR Quartile 1
JCR Impact 8.109
SJR Impact 6.058
Publication date 15/10/2019
ISI 000490140600013
DOI 10.1016/j.celrep.2019.09.013
Abstract 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-kappa B-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 beta 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.
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