2. Academic Validation
  3. 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

  • Cell Rep. 2020 May 26;31(8):107690. doi: 10.1016/j.celrep.2020.107690.
Xin Jin 1,  Wenxia Zhang 1,  Yang Wang 1,  Jia Liu 1,  Fengqi Hao 1,  Yunlong Li 1,  Miaomiao Tian 1,  Hengyao Shu 1,  Jiaxin Dong 1,  Yunpeng Feng 2,  Min Wei 3
Affiliations

Affiliations

  • 1 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.
  • 2 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. Electronic address: fengyp0108@nenu.edu.cn.
  • 3 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. Electronic address: weim750@nenu.edu.cn.
PMID: 32460017 DOI: 10.1016/j.celrep.2020.107690
Abstract

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.

Keywords

IL-12; JNK; K433 acetylation; PKM2; dendritic cell.

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