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

Author

Listed:
  • Tao Yu

    (University of Chinese Academy of Sciences)

  • Shucheng Gan

    (University of Chinese Academy of Sciences)

  • Qingchen Zhu

    (University of Chinese Academy of Sciences)

  • Dongfang Dai

    (The Affiliated Hospital of Jiangsu University)

  • Ni Li

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Hui Wang

    (Shanghai Jiaotong University School of Medicine)

  • Xiaosong Chen

    (Shanghai Jiaotong University School of Medicine)

  • Dan Hou

    (University of Chinese Academy of Sciences)

  • Yan Wang

    (University of Chinese Academy of Sciences)

  • Qiang Pan

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Jing Xu

    (University of Chinese Academy of Sciences)

  • Xingli Zhang

    (University of Chinese Academy of Sciences)

  • Junli Liu

    (University of Chinese Academy of Sciences)

  • Siyu Pei

    (University of Chinese Academy of Sciences)

  • Chao Peng

    (Zhangjiang Lab)

  • Ping Wu

    (Zhangjiang Lab)

  • Simona Romano

    (University of Naples, Federico II)

  • Chaoming Mao

    (The Affiliated Hospital of Jiangsu University)

  • Mingzhu Huang

    (Fudan University Shanghai Cancer Center)

  • Xiaodong Zhu

    (Fudan University Shanghai Cancer Center)

  • Kunwei Shen

    (Shanghai Jiaotong University School of Medicine)

  • Jun Qin

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Yichuan Xiao

    (University of Chinese Academy of Sciences)

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.

Suggested Citation

  • Tao Yu & Shucheng Gan & Qingchen Zhu & Dongfang Dai & Ni Li & Hui Wang & Xiaosong Chen & Dan Hou & Yan Wang & Qiang Pan & Jing Xu & Xingli Zhang & Junli Liu & Siyu Pei & Chao Peng & Ping Wu & Simona R, 2019. "Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12384-2
    DOI: 10.1038/s41467-019-12384-2
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