Figure 2 3.1 Regulating peripheral CD4 + T cell differentiation via epigenetic regulation As a metabolite of intracellular glutaminolysis, -KG not only participates in the TCA cycle and the generation of other amino acids, but also participates in the regulation of histone and DNA methylation levels as a cofactor of peroxidase, thus participating in the regulation of gene expression in cells ( + T cells even inhibited the expression of Foxp3 under the condition of Treg cells ( + T cells into Th1 cells and increases the generation of Foxp3 + Treg cells, and this effect can be reversed by the -KG analogue ( + T cells led to the reduced expression of PIK3IP1,a negative regulator of mTORC1, further leading to the activation of mTORC1 to promote the differentiation of effector Th1 cells ( 3.2 Regulating peripheral CD4 + T cell differentiation via mTORC1 The activity of mTORC1 plays an important role in integrating the metabolic spectrum and guiding the fate decision of CD4 + T cells because it senses and integrates multiple signals from the environment to control metabolism ( + T cells suppressed the differentiation of Th1 cells by reducing the response to IL-12 and preventing T-bet transcription ( + T cells showed enhanced phosphorylated STAT6 level in response to IL-4 (Th2 cell polarization factor), which further increased the transcription level of GATA3 in cell nuclear, thus promoting the differentiation of Th2 cells ( + T cells, which is required for the RORt genes expression ( via inducing HIF-1, but Treg cells is less dependent on glycolytic metabolic procedure to provide energy compared with Th17 cells, thus leading to a significant difference in the differentiation of Th17 and Treg cells ( Amino acids play an important role in the activation of mTORC1 signaling pathway, especially Gln, leucine (Leu), arginine (Arg) and methionine (Met) ( + T cells reduced the differentiation of Th1 and Th17 cells by attenuating the uptake of Gln and Leu to suppress mTORC1 activation ( + T cells by regulating mTORC1
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PMID: 23950538
Therefore, both prophylactic and therapeutic strategies of bilirubin administration are being considered
