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

TY - JOUR

T1 - The proliferation of human mucosal-associated invariant T cells requires a MYC-SLC7A5-glycolysis metabolic axis

AU - Kedia-Mehta, Nidhi

AU - Pisarska, Marta M.

AU - Rollings, Christina

AU - O'Neill, Chloe

AU - De Barra, Conor

AU - Foley, Cathriona

AU - Wood, Nicole A. W.

AU - Wrigley-Kelly, Neil

AU - Veerapen, Natacha

AU - Besra, Gurdyal

AU - Bergin, Ronan

AU - Jones, Nicholas

AU - O'Shea, Donal

AU - Sinclair, Linda V.

AU - Hogan, Andrew E.

N1 - Funding Information: This study was supported by the National Children’s Research Centre. N.K.-M.is supported by Health Research Board (ILP-POR-2019-110). C.D.B.is supported by a fellowship from the Irish Research Council. Financial support for Attune NxT was provided to Maynooth University Department of Biology by Science Foundation Ireland (16/RI/3399). L. V. S. and the proteomic research was supported by a Wellcome Trust Principle Research Fellowship (205023/Z/16/Z) and Equipment Award to D. A. Cantrell (202950/Z/16/Z). Copyright: © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

PY - 2023/4/18

Y1 - 2023/4/18

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85152863762

U2 - 10.1126/scisignal.abo2709

DO - 10.1126/scisignal.abo2709

M3 - Article

C2 - 37071733

SN - 1937-9145

VL - 16

JO - Science Signaling

JF - Science Signaling

IS - 781

M1 - eabo2709

ER -