MicroRNAs of the miR-17~92 family maintain adipose tissue macrophage homeostasis by sustaining IL-10 expression

  1. Xiang Zhang
  2. Jianguo Liu
  3. Li Wu
  4. Xiaoyu Hu  Is a corresponding author
  1. Tsinghua University, China
  2. Saint Louis University, United States

Abstract

Macrophages are critically involved in not only immune and inflammatory responses but also in maintenance of metabolic fitness of organisms. Combined genetic deficiency of three clusters in the miR-17~92 family drastically shifted macrophage phenotypes towards 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.

Data availability

Sequencing data have been deposited in GEO under accession code GSE129613 and GSE158627.

The following data sets were generated

Article and author information

Author details

  1. Xiang Zhang

    Institute for Immunology, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Jianguo Liu

    Department of Internal Medicine,, Saint Louis University, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Li Wu

    Institute for Immunology, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Xiaoyu Hu

    Institute for Immunology, Tsinghua University, Beijing, China
    For correspondence
    xiaoyuhu@tsinghua.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4289-6998

Funding

National Natural Science Foundation of China (31821003)

  • Xiaoyu Hu

National Natural Science Foundation of China (31725010)

  • Xiaoyu Hu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments using mice were approved by the Institutional Animal Care and Use Committees at Tsinghua University (Protocol #17-HXY1).

Reviewing Editor

  1. Florent Ginhoux, Agency for Science Technology and Research, Singapore

Publication history

  1. Received: February 2, 2020
  2. Accepted: November 4, 2020
  3. Accepted Manuscript published: November 5, 2020 (version 1)
  4. Version of Record published: November 19, 2020 (version 2)
  5. Version of Record updated: December 14, 2020 (version 3)

Copyright

© 2020, Zhang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Xiang Zhang
  2. Jianguo Liu
  3. Li Wu
  4. Xiaoyu Hu
(2020)
MicroRNAs of the miR-17~92 family maintain adipose tissue macrophage homeostasis by sustaining IL-10 expression
eLife 9:e55676.
https://doi.org/10.7554/eLife.55676
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