PMID- 32460017 OWN - NLM STAT- MEDLINE DCOM- 20210521 LR - 20210521 IS - 2211-1247 (Electronic) VI - 31 IP - 8 DP - 2020 May 26 TI - Pyruvate Kinase M2 Promotes the Activation of Dendritic Cells by Enhancing IL-12p35 Expression. PG - 107690 LID - S2211-1247(20)30643-4 [pii] LID - 10.1016/j.celrep.2020.107690 [doi] AB - 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. CI - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Jin, Xin AU - Jin X AD - 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. FAU - Zhang, Wenxia AU - Zhang W AD - 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. FAU - Wang, Yang AU - Wang Y AD - 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. FAU - Liu, Jia AU - Liu J AD - 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. FAU - Hao, Fengqi AU - Hao F AD - 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. FAU - Li, Yunlong AU - Li Y AD - 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. FAU - Tian, Miaomiao AU - Tian M AD - 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. FAU - Shu, Hengyao AU - Shu H AD - 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. FAU - Dong, Jiaxin AU - Dong J AD - 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. FAU - Feng, Yunpeng AU - Feng Y AD - 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. FAU - Wei, Min AU - Wei M AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 RN - 0 (Interleukin-12 Subunit p35) RN - EC 2.7.1.40 (Pyruvate Kinase) SB - IM MH - Dendritic Cells/*metabolism MH - Humans MH - Interleukin-12 Subunit p35/*metabolism MH - Pyruvate Kinase/*metabolism OTO - NOTNLM OT - IL-12 OT - JNK OT - K433 acetylation OT - PKM2 OT - dendritic cell COIS- Declaration of Interests The authors declare no competing interests. EDAT- 2020/05/28 06:00 MHDA- 2021/05/22 06:00 CRDT- 2020/05/28 06:00 PHST- 2019/10/10 00:00 [received] PHST- 2020/03/06 00:00 [revised] PHST- 2020/05/01 00:00 [accepted] PHST- 2020/05/28 06:00 [entrez] PHST- 2020/05/28 06:00 [pubmed] PHST- 2021/05/22 06:00 [medline] AID - S2211-1247(20)30643-4 [pii] AID - 10.1016/j.celrep.2020.107690 [doi] PST - ppublish SO - Cell Rep. 2020 May 26;31(8):107690. doi: 10.1016/j.celrep.2020.107690.