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TET2 Regulates the Neuroinflammatory Response in Microglia

Authors :
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
Source :
Cell Reports, Vol 29, Iss 3, Pp 697-713.e8 (2019)
Publication Year :
2019
Publisher :
Elsevier, 2019.

Abstract

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

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
22111247
Volume :
29
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.62cc26b45324c4b9b6bb3e90ee196ca
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2019.09.013