An NF-kappa B-microRNA regulatory network tunes macrophage inflammatory responses

作者:Mann Mati*; Mehta Arnav; Zhao Jimmy L; Lee Kevin; Marinov Georgi K; Garcia Flores Yvette; Baltimore David*
来源:Nature Communications, 2017, 8(1): 851.
DOI:10.1038/s41467-017-00972-z

摘要

The innate inflammatory response must be tightly regulated to ensure effective immune protection. NF-kappa B 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-kappa B activity in mouse macrophages. Elevated miR-155 expression potentiates NF-kappa B 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-kappa B 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-kappa B activity. This miRNA-based regulatory network enables a robust yet time-limited inflammatory response essential for functional immunity.

  • 出版日期2017-10-11