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. 2021 Feb 1;13(3):545. doi: 10.3390/cancers13030545

Figure 3.

Figure 3

Role of DNA methylation in regulating differentiation and activation of naïve CD4+ T cells into effector cells including Th1, Th2, Th17, and Tregs subtypes. DNA methylation changes during differentiation can lead to formation of subtypes of CD4+ T cells. The black boxes are cytokines that help in the differentiation and activation process for each subtype. For instance, Th1 are formed when naïve CD4+ T cells are stimulated by IL-12 and IFNγ cytokines and the IFNγ gene promoter remains hypomethylated and IFNγ is highly expressed. For the Th2 subtype, the IL-4 gene is demethylated and is highly expressed, whereas IFNγ is methylated and repressed. For Th17 cells, the IL-17 gene is demethylated and highly expressed. For Tregs, FOXP3 is demethylated at various regions, including promoter and enhancer, thereby markedly increasing FOXP3 expression. These methylation levels are maintained by DNMT1, DNMT3A, and TET2. The green boxes indicate the cytokines released from differentiated cells. These immune cells and released cytokines can further lead to tumor progression or suppression.