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Cited by 46Immune cells in cancerAtherosclerosis and Cardiovascular DiseasesGut microbiota and health

LncRNA lncLy6C induced by microbiota metabolite butyrate promotes differentiation of Ly6Chigh to Ly6Cint/neg macrophages through lncLy6C/C/EBPβ/Nr4A1 axis

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Gao, Yunhuan, Zhou, Jiang, Qi, Houbao, Wei, Jianmei, Yang, Yazheng, Yue, Jianmei, Liu, Xinqi, Zhang, Yuan +1 more·2020·Cell Discovery
DOI 10.1038/s41421-020-00211-8PMC PMC7683537
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Abstract

Macrophages are mainly divided into two populations, which play a different role in physiological and pathological conditions. The differentiation of these cells may be regulated by transcription factors. However, it is unclear how to modulate these transcription factors to affect differentiation of these cells. Here, we found that lncLy6C, a novel ultraconserved lncRNA, promotes differentiation of Ly6C high inflammatory monocytes into Ly6C low/neg resident macrophages. We demonstrate that gut microbiota metabolites butyrate upregulates the expression of lncLy6C. LncLy6C deficient mice had markedly increased Ly6C high pro-inflammatory monocytes and reduced Ly6C neg resident macrophages. LncLy6C not only bound with transcription factor C/EBPβ but also bound with multiple lysine methyltransferases of H3K4me3 to specifically promote the enrichment of C/EBPβ and H3K4me3 marks on the promoter region of Nr4A1, which can promote Ly6C high into Ly6C neg macrophages. As a result, lncLy6C causes the upregulation of Nr4A1 to promote Ly6C high inflammatory monocytes to differentiate into Ly6C int/neg resident macrophages.

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Sorted by citations

Authors
Gao, Y., Zhou, J., Qi, H., Wei, J., Yang, Y., Yue, J., Liu, X., Zhang, Y., & Yang, R.
Affiliations
Nankai University (CN)
Corresponding author
Yang, Rongcun
ORCID
Venue
Cell Discovery
Publisher
Springer Science and Business Media LLC
Published
2020-11-24
Volume
6
Issue
1
Pages
87-87
ISSN
2056-5968 (ISSN-L)
DOI
10.1038/s41421-020-00211-8
PMC
PMC7683537
OpenAlex
W3110054485
Cited by
46
References
6
Citations by year
2026: 4 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 5 · 2021: 9 · 2020: 1
FWCI
2.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Discovery (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (91442111, 91029736, 81970488, 9162910, 91842302, 31570114, 2016YFC1303604)
  • Nankai University (63191724)
  • State Key Laboratory of Medicinal Chemical Biology (63191724)
  • Tianjin Municipal Science and Technology Bureau (18JCZDJC35300)
  • National Key Research and Development Program of China (2016YFC1303604)
  • Fundamental Research Funds for the Central Universities
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
long non-coding RNA, Ly6C, macrophage differentiation, inflammatory monocytes, tissue-resident macrophages, butyrate, gut microbiota metabolites, C/EBPβ, Nur77, H3K4me3, lysine methyltransferase, transcriptional regulation

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