Pariollaud, M; Gibbs, JE; Hopwood, TW; Brown, S; Begley, N; Vonslow, R; Poolman, T; ... Ray, DW; + view all Pariollaud, M; Gibbs, JE; Hopwood, TW; Brown, S; Begley, N; Vonslow, R; Poolman, T; Guo, B; Saer, B; Jones, DH; Tellam, JP; Bresciani, S; Tomkinson, NCO; Wojno-Picon, J; Cooper, AWJ; Daniels, DA; Trump, RP; Grant, D; Zuercher, W; Willson, TM; MacDonald, AS; Bolognese, B; Podolin, PL; Sanchez, Y; Loudon, AS; Ray, DW; - view fewer (2018) Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation. Journal of Clinical Investigation , 128 (6) pp. 2281-2296. 10.1172/JCI93910.

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Abstract

There is a strong variation in pulmonary inflammation depending on the time of day. Airway epithelial cells have been shown to mediate rhythmic inflammatory responses, and loss of the central clock component BMAL1 in airway epithelium augments inflammation. It is not clear how BMAL1 regulates lung inflammation; however, REV-ERB transcription factors, have been proposed to regulate immune function downstream of BMAL1. In this episode, David Ray, Marie Pariollaud and colleagues provide evidence that REV-ERBα couples the pulmonary clock to innate immunity. Inflammatory stimuli were shown to promote REV-ERBα degradation, and complete lack of REV-ERBα further enhanced inflammation in the lungs in following inflammatory challenge. Together, these results identify REV-ERBα as a regulator of rhythmic inflammatory responses in the lung and provide rationale for further exploration of REV-ERBα as a target for inflammatory disease.

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