2. Academic Validation
  3. Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation

Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation

  • Cell Rep. 2022 Nov 29;41(9):111741. doi: 10.1016/j.celrep.2022.111741.
Chen Chen 1,  Weiqiao Zhang 1,  Tingyue Zhou 1,  Qiuyuan Liu 2,  Chao Han 3,  Zonghui Huang 4,  Si Chen 5,  Qiao Mei 2,  Cunjin Zhang 6,  Kaiguang Zhang 5,  Hongdi Ma 1,  Rongbin Zhou 7,  Wei Jiang 8,  Wen Pan 1,  Shu Zhu 9
Affiliations

Affiliations

  • 1 Department of Digestive Disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Institute of Immunology, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
  • 2 Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
  • 3 Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
  • 4 Institute of Immunology, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
  • 5 Department of Digestive Disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
  • 6 Department of Neurology, Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, Nanjing 210008, China.
  • 7 Institute of Immunology, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China.
  • 8 Institute of Immunology, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China. Electronic address: ustcjw@ustc.edu.cn.
  • 9 Department of Digestive Disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Institute of Immunology, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; School of Data Science, University of Science and Technology of China, Hefei 230026, China; Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China. Electronic address: zhushu@ustc.edu.cn.
PMID: 36450257 DOI: 10.1016/j.celrep.2022.111741
Abstract

Metabolic rewiring is essential for Th17 cells' functional identity to sense and interpret environmental cues. However, the environmental metabolic checkpoints with specific regulation of Th17 cells, manifesting potential therapeutic opportunities to autoimmune diseases, remain largely unknown. Here, by screening more than one hundred compounds derived from intestinal microbes or diet, we found that vitamin B5 (VB5) restrains Th17 cell differentiation as well as related autoimmune diseases such as experimental autoimmune encephalomyelitis and colitis. Mechanistically, VB5 is catabolized into coenzyme A (CoA) in a pantothenate kinase (PANK)-dependent manner, and in turn, CoA binds to Pyruvate Kinase isoform 2 (PKM2) to impede its phosphorylation and nuclear translocation, thus inhibiting glycolysis and STAT3 phosphorylation. In humans, reduced serum VB5 levels are found in both IBD and MS patients. Collectively, our study demonstrates a role of VB5 in Th17 cell metabolic reprograming, thus providing a potential therapeutic intervention for Th17 cell-associated autoimmune diseases.

Keywords

CP: Immunology; CP: Microbiology; CoA; PKM2; Th17; glucose metabolism; vitamin B5.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z