MicroRNAs of the miR-17~9 family maintain adipose tissue macrophage homeostasis by sustaining IL-10 expression.
Xiang ZhangJianguo LiuLi WuXiaoyu HuPublished in: eLife (2020)
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.
Keyphrases
- cell proliferation
- long non coding rna
- adipose tissue
- transcription factor
- poor prognosis
- long noncoding rna
- insulin resistance
- anti inflammatory
- genome wide
- type diabetes
- gene expression
- rheumatoid arthritis
- acute myeloid leukemia
- physical activity
- metabolic syndrome
- oxidative stress
- bone marrow
- skeletal muscle
- binding protein
- multidrug resistant
- dna methylation
- dendritic cells
- immune response
- weight gain