TY - JOUR
AU1 - Lü, Silin
AU2 - Deng, Jiacheng
AU3 - Liu, Huiying
AU4 - Liu, Bo
AU5 - Yang, Juan
AU6 - Miao, Yutong
AU7 - Li, Jing
AU8 - Wang, Nan
AU9 - Jiang, Changtao
AU1 - Xu, Qingbo
AU1 - Wang, Xian
AU1 - Feng, Juan
AB - Inflammation mediated by activated T cells plays an important role in the initiation and progression of hyperhomocysteinemia −/− (HHcy)-accelerated atherosclerosis in ApoE mice. Homocysteine (Hcy) activates Tcells to secrete proinflammatory cytokines, especially interferon (IFN)-γ; however, the precise mechanisms remain unclear. Metabolic reprogramming is critical for T cell inflammatory activation and effector functions. Our previous study demonstrated that Hcy regulates T cell mitochondrial reprogramming by enhancing endoplasmic reticulum (ER)-mitochondria coupling. In this study, we further explored the impor- + + tant role of glycolysis-mediated metabolic reprogramming in Hcy-activated CD4 T cells. Mechanistically, Hcy-activated CD4 T cell increased the protein expression and activity of pyruvate kinase muscle isozyme 2 (PKM2), the final rate-limiting enzyme in glycolysis, via the phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin signaling pathway. Knockdown of PKM2 by small interfering RNA reduced Hcy-induced CD4 Tcell IFN-γ secretion. Furthermore, we generated T cell-specific fl/fl PKM2 knockout mice by crossing LckCre transgenic mice with PKM2 mice and observed that Hcy-induced glycolysis and oxidative phosphorylation were both diminished in PKM2-deficient CD4 T cells with reduced glucose and lipid metabolites, −/− and subsequently reduced IFN-γ secretion. Tcell-depleted apolipoprotein E-deficient (ApoE ) mice adoptively transferred with PKM2-deficient CD4 Tcells, compared to mice transferred with control 
TI - PKM2-dependent metabolic reprogramming in CD4+ T cells is crucial for hyperhomocysteinemia-accelerated atherosclerosis
JF - Journal of Molecular Medicine
DO - 10.1007/s00109-018-1645-6
DA - 2018-05-07
UR - https://www.deepdyve.com/lp/springer-journals/pkm2-dependent-metabolic-reprogramming-in-cd4-t-cells-is-crucial-for-7JgKhTKTfi
SP - 585
EP - 600
VL - 96
IS - 6
DP - DeepDyve
ER -