@phdthesis{oai:oist.repo.nii.ac.jp:00002921,
 author = {Huang, Tsung-Yen},
 month = {2023-05-11, 2023-05-11},
 note = {Aerobic glycolysis, a metabolic pathway essential for effector T cell survival and proliferation, regulates the differentiation of autoimmune T helper (Th)17 cells, but the mechanism underlying this regulation is largely unknown. Here, we identify a glycolytic intermediate metabolite, phosphoenolpyruvate (PEP), as a negative regulator of Th17 differentiation. PEP supplementation or inhibition of downstream glycolytic enzymes in differentiating Th17 cells increases intracellular PEP levels and inhibits the expression of Th17 signature molecules, such as IL-17A. However, PEP supplementation does not significantly affect metabolic reprogramming, cell proliferation, and survival of differentiating Th17 cells. Mechanistically, PEP regulates the JunB-dependent pathogenic Th17 transcriptional program by inhibiting the DNA-binding activity of the JunB/BATF/IRF4 complex. Furthermore, daily administration of PEP to mice inhibits the generation of Th17 cells and ameliorates Th17-dependent autoimmune encephalomyelitis. These data demonstrate that PEP links aerobic glycolysis to the JunB-dependent pathogenic Th17 transcriptional program, suggesting the therapeutic potential of PEP for autoimmune diseases.},
 school = {Okinawa Institute of Science and Technology Graduate University},
 title = {ホスホエノールピルビン酸はJunBに依存するTh17の転写プログラムを制御する},
 year = {}
}