Pyruvate Kinase M2 Promotes the Activation of Dendritic Cells by Enhancing IL-12p35 Expression
Pyruvate Kinase M2 Promotes the Activation of Dendritic Cells by Enhancing IL-12p35 Expression
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丙酮酸激酶 M2 通过增强 IL-12p35 表达促进树突状细胞活化
DOI：
10.1016/j.celrep.2020.107690
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发表时间：
2020-05-26
期刊：
影响因子：
8.8
通讯作者：
Wei, Min
中科院分区：
文献类型：
--
作者：
Jin, Xin;Zhang, Wenxia;Wei, Min
树突状细胞（Dendritic cells，DCs）在先天性免疫和适应性免疫中发挥着重要作用。新出现的证据已经证明了DC激活期间的代谢重编程。然而，DC激活如何与代谢重编程联系仍不清楚。在这里，我们表明，丙酮酸激酶M2（PKM 2），糖酵解的最后一步的限速酶，是LPS诱导的DC激活的关键。在DC活化后，JNK信号刺激p300与PKM 2的结合，用于赖氨酸433的乙酰化，这是PKM 2不稳定和核重新定位的关键的经典翻译后修饰。随后，核PKM 2与c-Rel合作以增强II 12 p35表达，这对于Th 1细胞分化是重要的。同时，由于去四聚体导致PKM 2酶活性降低，促进糖酵解和脂肪酸合成，帮助DC满足其对生物大分子的需求。我们共同为DC激活的代谢控制提供了证据，并为由于Th 1功能失调而导致的异常免疫反应提供了见解。
Dendritic cells (DCs) play a central role in both innate and adaptive immunity. Emerging evidence has demonstrated metabolic reprogramming during DC activation. However, how DC activation is linked with metabolic reprogramming remains unclear. Here we show that pyruvate kinase M2 (PKM2), the rate-limiting enzyme in the last step of glycolysis, is critical for LPS-induced DC activation. Upon DC activation, JNK signaling stimulated p300 association with PKM2 for the acetylation of lysine 433, a classic post translational modification critical for PKM2 destabilization and nuclear re-localization. Subsequently, nuclear PKM2 partnered with c-Rel to enhance II12p35 expression, which is important for Th1 cell differentiation. Meanwhile, decreased enzymatic activity of PKM2 due to detetramerization facilitated glycolysis and fatty acid synthesis, helping DCs meet their need for biomacromolecules. Together, we provide evidence for metabolic control of DC activation and offer insights into aberrant immune responses due to dysregulated Th1 functions.