An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses Journal Article
| Authors: | Mann, M.; Mehta, A.; Zhao, J. L.; Lee, K.; Marinov, G. K.; Garcia-Flores, Y.; Lu, L. F.; Rudensky, A. Y.; Baltimore, D. |
| Article Title: | An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses |
| Abstract: | The innate inflammatory response must be tightly regulated to ensure effective immune protection. NF-κB is a key mediator of the inflammatory response, and its dysregulation has been associated with immune-related malignancies. Here, we describe a miRNA-based regulatory network that enables precise NF-κB activity in mouse macrophages. Elevated miR-155 expression potentiates NF-κB activity in miR-146a-deficient mice, leading to both an overactive acute inflammatory response and chronic inflammation. Enforced miR-155 expression overrides miR-146a-mediated repression of NF-κB activation, thus emphasizing the dominant function of miR-155 in promoting inflammation. Moreover, miR-155-deficient macrophages exhibit a suboptimal inflammatory response when exposed to low levels of inflammatory stimuli. Importantly, we demonstrate a temporal asymmetry between miR-155 and miR-146a expression during macrophage activation, which creates a combined positive and negative feedback network controlling NF-κB activity. This miRNA-based regulatory network enables a robust yet time-limited inflammatory response essential for functional immunity. © 2017 The Author(s). |
| Keywords: | mus |
| Journal Title: | Nature Communications |
| Volume: | 8 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2017-10-11 |
| Start Page: | 851 |
| Language: | English |
| DOI: | 10.1038/s41467-017-00972-z |
| PROVIDER: | scopus |
| PMCID: | PMC5636846 |
| PUBMED: | 29021573 |
| DOI/URL: | |
| Notes: | Article -- Correction to the author list issued, see DOI: 10.1038/s41467-018-05720-5 -- Export Date: 2 November 2017 -- Source: Scopus |
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