ReferenceID 2926

Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation

Cell Rep

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 potentia

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Reference Id
2926
Evidence Id
19516
Core Evidence Id
19516
Source Reference Id
6251
Herb2 Reference Id
HBREF007048
Subject Paper Key
HBIN048044_36450257
Pubmed Id
36450257
Doi
10.1016/j.celrep.2022.111741
Paper Title
Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation
Paper 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.
Journal
Cell Rep
Publish Year
2022
Experiment Subject
human; patient
Experiment Type
Cell Experiment
Phenotype Related
Experimental Autoimmune Encephalomyelitis; Th17 Cell-associated Autoimmune Diseases; Autoimmune Diseases; Colitis
Paper Title Cn
Paper Title En
Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation
Bilingual Status
semi_complete