| Autor: |
Kedia-Mehta, Nidhi, Pisarska, Marta M., Rollings, Christina, O'Neill, Chloe, De Barra, Conor, Foley, Cathriona, Wood, Nicole A. W., Wrigley-Kelly, Neil, Veerapen, Natacha, Besra, Gurdyal, Bergin, Ronan, Jones, Nicholas, O'Shea, Donal, Sinclair, Linda V., Hogan, Andrew E. |
| Předmět: |
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| Zdroj: |
Science Signaling; 4/18/2023, Vol. 16 Issue 781, p1-13, 13p |
| Abstrakt: |
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. The master regulator of innate T cell metabolism: Mucosal associated invariant T (MAIT) cells are a type of innate-like T cells that are enriched in adipose, gut, and liver tissue and that recognize bacterial metabolites. Upon activation, they proliferate and produce cytokines to promote host defense. Kedia-Mehta et al. showed that MAIT proliferation depended on MYC-associated pathways involving amino acid transport and glycolysis. Furthermore, MAIT cells from patients with obesity showed disrupted function and engagement of these pathways. These findings demonstrate that the canonical metabolic pathways found in conventional T cells are active in MAIT cells and may be relevant to the development of MAIT cell-based therapies and the study of obesity. —AEB [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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