2. Academic Validation
  3. Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24

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

  • Nat Commun. 2019 Sep 25;10(1):4353. doi: 10.1038/s41467-019-12384-2.
Tao Yu 1,  Shucheng Gan 1,  Qingchen Zhu 1,  Dongfang Dai 2,  Ni Li 1 3,  Hui Wang 4,  Xiaosong Chen 4,  Dan Hou 1,  Yan Wang 1,  Qiang Pan 1 3,  Jing Xu 1,  Xingli Zhang 1,  Junli Liu 1,  Siyu Pei 1,  Chao Peng 5,  Ping Wu 5,  Simona Romano 6,  Chaoming Mao 2,  Mingzhu Huang 7,  Xiaodong Zhu 7,  Kunwei Shen 4,  Jun Qin 8 9,  Yichuan Xiao 10
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Tissue Microenvironment and Tumor, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
  • 2 Institute of Oncology and Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, 212001, China.
  • 3 CAS Center for Excellence in Molecular Cell Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • 4 Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
  • 5 National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai, 201210, China.
  • 6 Department of Molecular Medicine and Medical Biotechnology, University of Naples, Federico II, 5-80131, Naples, Italy.
  • 7 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 8 CAS Key Laboratory of Tissue Microenvironment and Tumor, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China. qinjun@sibs.ac.cn.
  • 9 CAS Center for Excellence in Molecular Cell Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. qinjun@sibs.ac.cn.
  • 10 CAS Key Laboratory of Tissue Microenvironment and Tumor, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China. ycxiao@sibs.ac.cn.
PMID: 31554795 DOI: 10.1038/s41467-019-12384-2
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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