2. Academic Validation
  3. MEF2C promotes M1 macrophage polarization and Th1 responses

MEF2C promotes M1 macrophage polarization and Th1 responses

  • Cell Mol Immunol. 2022 Apr;19(4):540-553. doi: 10.1038/s41423-022-00841-w.
Xibao Zhao  # 1,  Qianqian Di  # 1,  Han Liu  # 2,  Jiazheng Quan 1,  Jing Ling 3,  Zizhao Zhao 3,  Yue Xiao 1,  Han Wu 1,  Zherui Wu 1,  Wengang Song 4,  Huazhang An 5,  Weilin Chen 6
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China.
  • 2 Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.
  • 3 Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 4 Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jingshi Road 16766, Jinan, Shandong, 250014, China.
  • 5 Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jingshi Road 16766, Jinan, Shandong, 250014, China. anhz@immunol.org.
  • 6 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China. cwl@szu.edu.cn.
  • # Contributed equally.
PMID: 35194174 DOI: 10.1038/s41423-022-00841-w
Abstract

The polarization of macrophages to the M1 or M2 phenotype has a pivotal role in inflammation and host defense; however, the underlying molecular mechanism remains unclear. Here, we show that myocyte enhancer factor 2 C (MEF2C) is essential for regulating M1 macrophage polarization in response to Infection and inflammation. Global gene expression analysis demonstrated that MEF2C deficiency in macrophages downregulated the expression of M1 phenotypic markers and upregulated the expression of M2 phenotypic markers. MEF2C significantly promoted the expression of interleukin-12 p35 subunit (Il12a) and interleukin-12 p40 subunit (Il12b). Myeloid-specific Mef2c-knockout mice showed reduced IL-12 production and impaired Th1 responses, which led to susceptibility to Listeria monocytogenes Infection and protected against DSS-induced IBD in vivo. Mechanistically, we showed that MEF2C directly activated the transcription of Il12a and Il12b. These findings reveal a new function of MEF2C in macrophage polarization and Th1 responses and identify MEF2C as a potential target for therapeutic intervention in inflammatory and autoimmune diseases.

Keywords

Inflammation; Interleukin-12; Macrophage polarization; Myocyte enhancer factor 2C; T helper type 1 response.

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