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MEF2C promotes M1 macrophage polarization and Th1 responses

Cellular & Molecular Immunology volume 19, pages 540–553 (2022)Cite this article

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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.

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Acknowledgements

This work was supported by grants from the National Key Research and Development Program of China (2016YFA0502201) awarded to Prof. Huazhang An; the National Natural Science Foundation of China (Nos. U1801283, 31870908), the Guangdong Provincial Science and Technology Program (No. 2019B030301009) and the SZU Top Ranking Project (No. 86000000210) awarded to Prof. Weilin Chen; the National Natural Science Foundation of China (No. 81771711) awarded to Prof. Wengang Song; and the Guangdong Provincial Science and Technology Program (No. 2019A1515110086) awarded to Xibao Zhao. We thank Jessica Kate Tamanini (Scientific Editor, Shenzhen University School of Medicine) for editing the manuscript.

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  1. These authors contributed equally: Xibao Zhao, Qianqian Di, Han Liu.

Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China

    Xibao Zhao, Qianqian Di, Jiazheng Quan, Yue Xiao, Han Wu, Zherui Wu & Weilin Chen

  2. Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China

    Han Liu

  3. Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China

    Jing Ling & Zizhao Zhao

  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

    Wengang Song & Huazhang An

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Contributions

XZ, HA, and WC participated in the research design. XZ, QD, HL, and JQ conducted the experiments. JL, ZZ, WS, QD, YX, HW, and ZW contributed analytic tools or new reagents. XZ, WC, and HA performed the data analysis. XZ, WC, and HA contributed to the writing of the manuscript.

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Correspondence to Huazhang An or Weilin Chen.

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Zhao, X., Di, Q., Liu, H. et al. MEF2C promotes M1 macrophage polarization and Th1 responses. Cell Mol Immunol 19, 540–553 (2022). https://doi.org/10.1038/s41423-022-00841-w

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