Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation

Chen Chen¹, Weiqiao Zhang¹, Tingyue Zhou¹, Qiuyuan Liu², Chao Han³, Zonghui Huang⁴, Si Chen⁵, Qiao Mei², Cunjin Zhang⁶, Kaiguang Zhang⁵, Hongdi Ma¹, Rongbin Zhou⁷, Wei Jiang⁸, Wen Pan¹, Shu Zhu⁹

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

Free article

Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation

Chen Chen et al. Cell Rep. 2022.

Free article

. 2022 Nov 29;41(9):111741.

doi: 10.1016/j.celrep.2022.111741.

Authors

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.

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Conflict of interest statement

Declaration of interests S.Z., C.C., and W.Z. have filed a patent application on the role of vitamin B5 in the intervention of Th17-associated autoimmune diseases.

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Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation

Affiliations

Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation

Authors

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

Full Text Sources

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