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Title 

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

Authors 

J M YukT S KimS Y KimH M LeeJ HanC R DufourJ K KimH S JinC S YangK S ParkChul Ho LeeJ M KimG R KweonH S ChoiJ M VanackerD D MooreV GiguereE K Jo

Publisher 

Elsevier (Cell Press)

Issue Date 

2015

Citation 

Immunity, vol. 43, no. 1, pp. 80-91

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

Link 

http://dx.doi.org/10.1016/j.immuni.2015.07.003

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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