| First Author | Curtis AM | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 23 | Pages | 7231-6 |
| PubMed ID | 25995365 | Mgi Jnum | J:223291 |
| Mgi Id | MGI:5648640 | Doi | 10.1073/pnas.1501327112 |
| Citation | Curtis AM, et al. (2015) Circadian control of innate immunity in macrophages by miR-155 targeting Bmal1. Proc Natl Acad Sci U S A 112(23):7231-6 |
| abstractText | 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-kappaB 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. |
