The proliferation of human mucosal-associated invariant T cells requires a MYC-SLC7A5-glycolysis metabolic axis

Nidhi Kedia-Mehta, Marta M. Pisarska, Christina Rollings, Chloe O'Neill, Conor De Barra, Cathriona Foley, Nicole A. W. Wood, Neil Wrigley-Kelly, Natacha Veerapen, Gurdyal Besra, Ronan Bergin, Nicholas Jones, Donal O'Shea, Linda V. Sinclair (Lead / Corresponding author), Andrew E. Hogan (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
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Abstract

Mucosal-associated invariant T (MAIT) cells are an abundant population of innate T cells that recognize bacterial ligands and play a key role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells undergo proliferative expansion and increase their production of effector molecules such as cytokines. In this study, we found that both mRNA and protein abundance of the key metabolism regulator and transcription factor MYC was increased in stimulated MAIT cells. Using quantitative mass spectrometry, we identified the activation of two MYC-controlled metabolic pathways, amino acid transport and glycolysis, both of which were necessary for MAIT cell proliferation. Last, we showed that MAIT cells isolated from people with obesity showed decreased MYC mRNA abundance upon activation, which was associated with defective MAIT cell proliferation and functional responses. Collectively, our data uncover the importance of MYC-regulated metabolism for MAIT cell proliferation and provide additional insight into the molecular basis for the functional defects of MAIT cells in obesity.

Original languageEnglish
Article numbereabo2709
Number of pages13
JournalScience Signaling
Volume16
Issue number781
DOIs
Publication statusPublished - 18 Apr 2023

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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