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
Notes: Article -- Correction to the author list issued, see DOI: 10.1038/s41467-018-05720-5 -- Export Date: 2 November 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Alexander Rudensky
    115 Rudensky
  2. Jimmy Liu Zhao
    1 Zhao