Loading…
M1 polarization refers to the process by which macrophages adopt a pro-inflammatory phenotype, typically called "classically activated" macrophages. This polarization is usually induced by microbial products (like lipopolysaccharide) and Th1 cytokines (such as interferon-gamma), leading to increased production of inflammatory cytokines (e.g., Tumor Necrosis Factor alfa (TNF-alfa), Interleukin-1 (IL-1) beta (IL-1F2), Interleukin-6 (IL-6)), reactive oxygen and nitrogen species, and enhanced microbicidal and tumoricidal activity.
Myocyte enhancer factor 2 C (MEF2C) plays a crucial role in regulating M1 macrophage polarization in response to infection and inflammation. Studies on global gene expression have shown that when MEF2C is deficient in macrophages, there is a downregulation of M1 phenotypic markers and an upregulation of M2 phenotypic markers. MEF2C significantly enhances the expression of the interleukin-12 p35 subunit and the Interleukin-12 (IL-12) / Interleukin-23 (IL23) p40 subunit beta (Il12b). In mice with a myeloid-specific knockout of Mef2c, there is a noticeable reduction in IL-12 production and impaired Th1 responses, making them more susceptible to Listeria monocytogenes infection while providing protection against DSS-induced inflammatory bowel disease (IBD) in vivo. Mechanistically, it has been demonstrated that MEF2C directly activates the transcription of Il12a and Il12b. These findings uncover a novel function of MEF2C in macrophage polarization and Th1 responses, highlighting MEF2C as a potential target for therapeutic intervention in inflammatory and autoimmune diseases.