{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T17:34:46Z","timestamp":1786556086707,"version":"build-2736575974"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kathleen Lonsdale Institute for Human Health Research"},{"name":"St Vincent\u2019s Foundation"},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","award":["ILP-POR-2024-019"],"award-info":[{"award-number":["ILP-POR-2024-019"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Attune NxT"},{"name":"Seahorse Analyzer"},{"name":"Maynooth University Department of Biology by Science Foundation Ireland","award":["16\/RI\/3399"],"award-info":[{"award-number":["16\/RI\/3399"]}]},{"name":"MRC New Investigator Research Grant","award":["MR\/X000095\/1"],"award-info":[{"award-number":["MR\/X000095\/1"]}]},{"name":"Lister Institute Prize Fellow and was supported by the UK Medical Research Council","award":["MC_UU_00038\/8"],"award-info":[{"award-number":["MC_UU_00038\/8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that recognizes bacterial-derived antigens presented on MR1. Upon TCR triggering, MAIT cells respond rapidly, producing a range of effector molecules which facilitate host-protective responses in the context of microbial infections. In contrast, MAIT cell responses to viral infection are instead triggered by the recognition of cytokines, and occur independently of TCR engagement. The molecular and metabolic regulation of MAIT cell TCR responses is rapidly emerging, but there is a paucity of data on cytokine driven responses. Here, using high-resolution, quantitative proteomic analysis, we map the downstream proteome of innate cytokine (IL-18\/IFN\u03b1)\u2013activated MAIT cells, highlighting robust cytokine-driven remodeling and a signature that is distinct from the TCR-driven response. MAIT cells significantly increase protein biosynthesis in response to innate cytokine stimulation and rapidly upregulate the production of IFN\u03b3, granzyme B, and IFN-stimulated gene 15. We demonstrate the metabolic kinetics of MAIT cell responses to cytokine stimulation and highlight a rapid but transient glycolytic burst that is uncoupled from mitochondrial remodeling and contrasts the robust metabolic profile elicited downstream of TCR engagement. Finally, we demonstrate differential contributions from both glycogen and glucose in supporting MAIT cell responses to innate cytokines and further highlight the importance of nutrient availability as a governing signal for MAIT cell fitness and effector functioning.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag212","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:42:25Z","timestamp":1786552945000},"source":"Crossref","is-referenced-by-count":0,"title":["Rapid glycolytic metabolism underpins mucosal-associated invariant T cell functional responses to innate cytokines"],"prefix":"10.1093","volume":"215","author":[{"given":"Eimear K","family":"Ryan","sequence":"first","affiliation":[{"name":"Kathleen Lonsdale Institute for Human Health Research, Maynooth University , Maynooth, County Kildare,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Institute of Life Science, Swansea University Medical School , Swansea,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"Bergin","sequence":"additional","affiliation":[{"name":"Kathleen Lonsdale Institute for Human Health Research, Maynooth University , Maynooth, County Kildare,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael E","family":"Salazar","sequence":"additional","affiliation":[{"name":"Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee , Dundee,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cian","family":"Davis","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s University Hospital, University College Dublin , Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Kedia-Mehta","sequence":"additional","affiliation":[{"name":"Kathleen Lonsdale Institute for Human Health Research, Maynooth University , Maynooth, County Kildare,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Amini","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology and Liver Unit, Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford , Oxford,","place":["United Kingdom"]},{"name":"Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford , Oxford,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6461-252X","authenticated-orcid":false,"given":"Lucy C","family":"Garner","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology and Liver Unit, Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford , Oxford,","place":["United Kingdom"]},{"name":"Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford , Oxford,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciara","family":"Flynn","sequence":"additional","affiliation":[{"name":"Kathleen Lonsdale Institute for Human Health Research, Maynooth University , Maynooth, County Kildare,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin\u00e9ad","family":"Ryan","sequence":"additional","affiliation":[{"name":"Kathleen Lonsdale Institute for Human Health Research, Maynooth University , Maynooth, County Kildare,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Perry","sequence":"additional","affiliation":[{"name":"Institute of Life Science, Swansea University Medical School , Swansea,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne C","family":"Masterson","sequence":"additional","affiliation":[{"name":"Kathleen Lonsdale Institute for Human Health Research, Maynooth University , Maynooth, County Kildare,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Heneghan","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s University Hospital, University College Dublin , Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul N","family":"Moynagh","sequence":"additional","affiliation":[{"name":"Kathleen Lonsdale Institute for Human Health Research, Maynooth University , Maynooth, County Kildare,","place":["Ireland"]},{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast , Belfast,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirby N","family":"Swatek","sequence":"additional","affiliation":[{"name":"Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee , Dundee,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology and Liver Unit, Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford , Oxford,","place":["United Kingdom"]},{"name":"Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford , Oxford,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Jones","sequence":"additional","affiliation":[{"name":"Institute of Life Science, Swansea University Medical School , Swansea,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1248-7189","authenticated-orcid":false,"given":"Linda V","family":"Sinclair","sequence":"additional","affiliation":[{"name":"Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee , Dundee,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donal","family":"O\u2019Shea","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s University Hospital, University College Dublin , Dublin,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew E","family":"Hogan","sequence":"additional","affiliation":[{"name":"Kathleen Lonsdale Institute for Human Health Research, Maynooth University , Maynooth, County Kildare,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2026081212422271500_vkag212-B1","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nature01433","article-title":"Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1","volume":"422","author":"Treiner","year":"2003","journal-title":"Nature"},{"key":"2026081212422271500_vkag212-B2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nature11605","article-title":"MR1 presents microbial vitamin B metabolites to MAIT cells","volume":"491","author":"Kjer-Nielsen","year":"2012","journal-title":"Nature"},{"key":"2026081212422271500_vkag212-B3","doi-asserted-by":"crossref","first-page":"eabo2709","DOI":"10.1126\/scisignal.abo2709","article-title":"The proliferation of human mucosal-associated invariant T cells requires a MYC-SLC7A5-glycolysis metabolic 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