Orphan nuclear receptor ERRα controls macrophage metabolic signaling and A20 expression to negatively regulate TLR-induced inflammation

Cited 74 time in scopus
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Title
Orphan nuclear receptor ERRα controls macrophage metabolic signaling and A20 expression to negatively regulate TLR-induced inflammation
Author(s)
J M Yuk; T S Kim; S Y Kim; H M Lee; J Han; C R Dufour; J K Kim; H S Jin; C S Yang; K S Park; Chul Ho Lee; J M Kim; G R Kweon; H S Choi; J M Vanacker; D D Moore; V Giguere; E K Jo
Bibliographic Citation
Immunity, vol. 43, no. 1, pp. 80-91
Publication Year
2015
Abstract
The orphan nuclear receptor estrogen-related receptor α (ERRα; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRα negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERRα-deficient (Esrra-/-) mice showed increased susceptibility to endotoxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERRα regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra-/- macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERRα was required for the regulation of NF-κB signaling by controlling p65 acetylation via maintenance of NAD+ levels and sirtuin 1 activation. These findingsunravel a previously unappreciated role for ERRα as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming.
ISSN
1074-7613
Publisher
Elsevier-Cell Press
DOI
http://dx.doi.org/10.1016/j.immuni.2015.07.003
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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