Curtis, Anne M. and Fagundes, Caio T. and Yang, Guangrui and Palsson-McDermott, Eva M. and Wochal, Paulina and McGettrick, Anne F. and Foley, Niamh H. and Early, James O. and Chen, Lihong and Zhang, Hanrui and Xue, Chenyi and Geiger, Sarah S. and Hokamp, Karsten and Reilly, Muredach P. and Coogan, Andrew and Vigorito, Elena and Fitzgerald, Garret A. and O'Neill, Luke A.J. (2015) Circadian control of innate immunity in macrophages by miR-155 targeting Bmal1. Proceedings of the National Academy of Sciences, 112 (23). pp. 7231-7236. ISSN 1091-6490

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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.

Item Type:	Article
Additional Information:	The definitive version of this article is available at DOI: 10.1073/pnas.1501327112 . This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1501327112/-/DCSupplemental.
Keywords:	inflammation; sepsis; circadian clock; miR-155; Bmal1;
Academic Unit:	Faculty of Science and Engineering > Psychology
Item ID:	6185
Identification Number:	https://doi.org/10.1073/pnas.1501327112
Depositing User:	Dr. Andrew Coogan
Date Deposited:	12 Jun 2015 10:51
Journal or Publication Title:	Proceedings of the National Academy of Sciences
Publisher:	National Academy of Sciences
Refereed:	Yes
Funders:	European Research Council, Science Foundation Ireland (SFI), NIH, European Community Seventh Framework Programme, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil
URI:	http://www.pnas.org/
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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