Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation

Chen Chen1, Weiqiao Zhang1, Tingyue Zhou1

  • 1Department 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.

Cell Reports
|November 30, 2022
PubMed

Insights

Vitamin B5 (VB5) limits the differentiation of T helper 17 (Th17) cells and associated autoimmune diseases. This occurs by VB5

Area of Science:

  • Immunology
  • Metabolic pathways
  • Microbiome-diet interactions

Background:

  • Metabolic rewiring is crucial for T helper 17 (Th17) cell function.
  • Environmental metabolic checkpoints regulating Th17 cells are largely unknown, yet hold therapeutic potential for autoimmune diseases.

Purpose of the Study:

  • To identify environmental factors regulating Th17 cell differentiation.
  • To explore therapeutic strategies for Th17 cell-mediated autoimmune conditions.

Main Methods:

  • Screening of over 100 compounds from intestinal microbes and diet.
  • Investigating the mechanism of vitamin B5 (VB5) action on Th17 cells.
  • Assessing VB5 levels in human autoimmune disease patients.

Main Results:

  • Vitamin B5 (VB5) was identified as an inhibitor of Th17 cell differentiation and experimental autoimmune encephalomyelitis and colitis.
  • VB5 is metabolized to coenzyme A (CoA), which inhibits pyruvate kinase M2 (PKM2) phosphorylation and nuclear translocation, thereby suppressing glycolysis and STAT3 phosphorylation.
  • Reduced serum VB5 levels were observed in patients with inflammatory bowel disease (IBD) and multiple sclerosis (MS).

Conclusions:

  • VB5 plays a significant role in the metabolic reprogramming of Th17 cells.
  • VB5 represents a potential therapeutic agent for autoimmune diseases driven by Th17 cells.

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