Cassidy, Féaron C. and Kedia-Mehta, Nidhi and Bergin, Ronan and Woodcock, Andrea and Berisha, Ardena and Bradley, Ben and Booth, Eva and Jenkins, Benjamin J. and Ryan, Odhrán K. and Jones, Nicholas and Sinclair, Linda V. and O’Shea, Donal and Hogan, Andrew E. (2023) Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses. Proceedings of the National Academy of Sciences, 120 (25). ISSN 1091-6490

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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.

Item Type:	Article
Keywords:	MAIT cells; immunometabolism; cytotoxicity; Glycogen- fuelled metabolism; rapid mucosal- associated invariant T cell responses;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	17314
Identification Number:	https://doi.org/10.1073/pnas.2300566120
Depositing User:	Andrew Hogan
Date Deposited:	13 Jun 2023 09:51
Journal or Publication Title:	Proceedings of the National Academy of Sciences
Publisher:	National Academy of Sciences
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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