RT Journal Article
T1 TET2 Regulates the Neuroinflammatory Response in Microglia.
A1 Carrillo-Jimenez, Alejandro
A1 Deniz, Özgen
A1 Niklison-Chirou, Maria Victoria
A1 Ruiz, Rocio
A1 Bezerra-Salomão, Karina
A1 Stratoulias, Vassilis
A1 Amouroux, Rachel
A1 Yip, Ping Kei
A1 Vilalta, Anna
A1 Cheray, Mathilde
A1 Scott-Egerton, Alexander Michael
A1 Rivas, Eloy
A1 Tayara, Khadija
A1 García-Domínguez, Irene
A1 Garcia-Revilla, Juan
A1 Fernandez-Martin, Juan Carlos
A1 Espinosa-Oliva, Ana Maria
A1 Shen, Xianli
A1 St George-Hyslop, Peter
A1 Brown, Guy Charles
A1 Hajkova, Petra
A1 Joseph, Bertrand
A1 Venero, Jose Luis
A1 Branco, Miguel Ramos
A1 Burguillos, Miguel Angel
K1 TET2
K1 TLR-4
K1 epigenetics
K1 metabolism
K1 microglia
K1 neuroinflammation
AB 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.
YR 2019
FD 2019
LK http://hdl.handle.net/10668/14856
UL http://hdl.handle.net/10668/14856
LA en
DS RISalud
RD Apr 8, 2025