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Cited by 348Immune cells in cancerCytokine Signaling Pathways and InteractionsTGF-β signaling in diseases

Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24

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Yu, Tao, Gan, Shucheng, Zhu, Qingchen, Dai, Dongfang, Li, Ni, Wang, Hui, Chen, Xiaosong, Hou, Dan +15 more·2019·Nature Communications
DOI 10.1038/s41467-019-12384-2PMC PMC6761150
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Abstract

Stat6 is known to drive macrophage M2 polarization. However, how macrophage polarization is fine-tuned by Stat6 is poorly understood. Here, we find that Lys383 of Stat6 is acetylated by the acetyltransferase CREB-binding protein (CBP) during macrophage activation to suppress macrophage M2 polarization. Mechanistically, Trim24, a CBP-associated E3 ligase, promotes Stat6 acetylation by catalyzing CBP ubiquitination at Lys119 to facilitate the recruitment of CBP to Stat6. Loss of Trim24 inhibits Stat6 acetylation and thus promotes M2 polarization in both mouse and human macrophages, potentially compromising antitumor immune responses. By contrast, Stat6 mediates the suppression of TRIM24 expression in M2 macrophages to contribute to the induction of an immunosuppressive tumor niche. Taken together, our findings establish Stat6 acetylation as an essential negative regulatory mechanism that curtails macrophage M2 polarization.

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Authors
Yu, T., Gan, S., Zhu, Q., Dai, D., Li, N., Wang, H., Chen, X., Hou, D., Wang, Y., Pan, Q., Xu, J., Zhang, X., Liu, J., Pei, S., Peng, C., Wu, P., Romano, S., Mao, C., Huang, M., Zhu, X., Shen, K., Qin, J., & Xiao, Y.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • Affiliated Hospital of Jiangsu University (CN)
  • Shanghai Zhangjiang Laboratory (CN)
  • University of Naples Federico II (IT)
  • Fudan University (CN)
Corresponding author
  • Qin, Jun
  • Xiao, Yichuan
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-09-25
Volume
10
Issue
1
Pages
4353-4353
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-12384-2
PMC
PMC6761150
OpenAlex
W2977174403
Cited by
348
References
54
Citations by year
2026: 40 · 2025: 61 · 2024: 61 · 2023: 69 · 2022: 57 · 2021: 31 · 2020: 29
FWCI
11.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (81571545, 81770567)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
STAT6, TRIM24, M2 macrophage polarization, protein acetylation, CREB-binding protein, E3 ubiquitin ligase, macrophage activation, tumor-associated macrophages, antitumor immunity, immunosuppressive tumor microenvironment
MeSH terms
Acetylation, Animals, Gene Expression Regulation, Humans, Lysine, Macrophage Activation, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Neoplasms, Experimental, Nuclear Proteins, Transcription Factors, Cyclic AMP Response Element-Binding Protein, Mice, Knockout, Cell Line, Tumor, STAT6 Transcription Factor, HEK293 Cells

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