Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses

Féaron C. Cassidy, Nidhi Kedia-Mehta, Ronan Bergin, Andrea Woodcock, Ardena Berisha, Ben Bradley, Eva Booth, Benjamin J. Jenkins, Odhrán K. Ryan, Nicholas Jones, Linda V. Sinclair, Donal O'Shea, Andrew E. Hogan (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
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Abstract

Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells which recognize a limited repertoire of ligands presented by the MHC class-I like molecule MR1. In addition to their key role in host protection against bacterial and viral pathogens, MAIT cells are emerging as potent anti-cancer effectors. With their abundance in human, unrestricted properties, and rapid effector functions MAIT cells are emerging as attractive candidates for immunotherapy. In the current study, we demonstrate that MAIT cells are potent cytotoxic cells, rapidly degranulating and inducing target cell death. Previous work from our group and others has highlighted glucose metabolism as a critical process for MAIT cell cytokine responses at 18 h. However, the metabolic processes supporting rapid MAIT cell cytotoxic responses are currently unknown. Here, we show that glucose metabolism is dispensable for both MAIT cell cytotoxicity and early (<3 h) cytokine production, as is oxidative phosphorylation. We show that MAIT cells have the machinery required to make (GYS-1) and metabolize (PYGB) glycogen and further demonstrate that that MAIT cell cytotoxicity and rapid cytokine responses are dependent on glycogen metabolism. In summary, we show that glycogen-fueled metabolism supports rapid MAIT cell effector functions (cytotoxicity and cytokine production) which may have implications for their use as an immunotherapeutic agent.
Original languageEnglish
Article numbere2300566120
Number of pages7
JournalProceedings of the National Academy of Sciences
Volume120
Issue number25
Early online date12 Jun 2023
DOIs
Publication statusPublished - 20 Jun 2023

Keywords

  • Mucosal associated invariant T cells
  • Metabolism
  • Glycogen
  • Cytotoxicity

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