Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), Northeast Normal University, 5268 Renmin Street, Changchun, Jilin, 130024, People's Republic of China.
Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), Northeast Normal University, 5268 Renmin Street, Changchun, Jilin, 130024, People's Republic of China.
Cell Rep. 2020 May 26;31(8):107690. doi: 10.1016/j.celrep.2020.107690.
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 posttranslational modification critical for PKM2 destabilization and nuclear re-localization. Subsequently, nuclear PKM2 partnered with c-Rel to enhance Il12p35 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.
树突状细胞 (DCs) 在固有免疫和适应性免疫中发挥核心作用。新出现的证据表明，DC 激活过程中存在代谢重编程。然而，DC 激活与代谢重编程之间的联系尚不清楚。在这里，我们表明，糖酵解最后一步的限速酶丙酮酸激酶 M2 (PKM2) 对于 LPS 诱导的 DC 激活至关重要。在 DC 激活后，JNK 信号刺激 p300 与 PKM2 结合，导致赖氨酸 433 乙酰化，这是 PKM2 不稳定和核重新定位的关键翻译后修饰。随后，核 PKM2 与 c-Rel 合作增强 Il12p35 的表达，这对于 Th1 细胞分化很重要。同时，由于四聚化导致 PKM2 的酶活性降低，促进了糖酵解和脂肪酸合成，帮助 DC 满足其对生物大分子的需求。总之，我们为 DC 激活的代谢控制提供了证据，并为由于 Th1 功能失调导致的异常免疫反应提供了新的见解。
