First Author | Zhang X | Year | 2020 |
Journal | Elife | Volume | 9 |
PubMed ID | 33150865 | Mgi Jnum | J:298686 |
Mgi Id | MGI:6477113 | Doi | 10.7554/eLife.55676 |
Citation | Zhang X, et al. (2020) MicroRNAs of the miR-17~9 family maintain adipose tissue macrophage homeostasis by sustaining IL-10 expression. Elife 9:e55676 |
abstractText | Macrophages are critically involved in not only immune and inflammatory responses but also maintenance of metabolic fitness of organisms. Combined genetic deficiency of three clusters in the miR-17~92 family drastically shifted macrophage phenotypes toward the inflammatory spectrum characterized by heightened production of pro-inflammatory mediator TNF and diminished expression of anti-inflammatory cytokine IL-10. Consequently, macrophages residing in the adipose tissues from myeloid-specific miRNA triple knockout mice spontaneously developed inflammatory phenotypes and displayed alterations of overall physiological conditions as evidenced by obesity and compromised glucose tolerance. Mechanistically, miR-17~92 family miRNAs sustained IL-10 production by promoting transcription of the Fos gene, which is secondary to downregulation of Fos by transcription factor YY1, a direct target of miR-17~92 family miRNAs. Together, these results identified miR-17~92 family miRNAs as crucial regulators of the balance between pro- and anti-inflammatory cytokines and exemplified how macrophage-intrinsic regulatory circuit exerted impactful influence on general physiology. |