Title: Circadian control of innate immunity in macrophages by miR-155 targeting Bmal1.

Authors: Curtis, Anne M; Fagundes, Caio T; Yang, Guangrui; Palsson-McDermott, Eva M; Wochal, Paulina; McGettrick, Anne F; Foley, Niamh H; Early, James O; Chen, Lihong; Zhang, Hanrui; Xue, Chenyi; Geiger, Sarah S; Hokamp, Karsten; Reilly, Muredach P; Coogan, Andrew N; Vigorito, Elena; FitzGerald, Garret A; O'Neill, Luke A J

Published In Proc Natl Acad Sci U S A, (2015 Jun 09)

Abstract: The response to an innate immune challenge is conditioned by the time of day, but the molecular basis for this remains unclear. In myeloid cells, there is a temporal regulation to induction by lipopolysaccharide (LPS) of the proinflammatory microRNA miR-155 that correlates inversely with levels of BMAL1. BMAL1 in the myeloid lineage inhibits activation of NF-κB and miR-155 induction and protects mice from LPS-induced sepsis. Bmal1 has two miR-155-binding sites in its 3'-UTR, and, in response to LPS, miR-155 binds to these two target sites, leading to suppression of Bmal1 mRNA and protein in mice and humans. miR-155 deletion perturbs circadian function, gives rise to a shorter circadian day, and ablates the circadian effect on cytokine responses to LPS. Thus, the molecular clock controls miR-155 induction that can repress BMAL1 directly. This leads to an innate immune response that is variably responsive to challenges across the circadian day.

PubMed ID: 25995365

MeSH Terms: 3' Untranslated Regions; ARNTL Transcription Factors/genetics; ARNTL Transcription Factors/physiology*; Adipose Tissue/metabolism; Animals; Circadian Rhythm*; Cytokines/biosynthesis; Immunity, Innate*; Macrophages/immunology*; Macrophages/metabolism; Mice; Mice, Knockout; MicroRNAs/physiology*; NF-kappa B/metabolism