Hope, HC, Pickersgill, G, Ginefra, P et al. (3 more authors) (2022) TGFβ limits Myc-dependent TCR-induced metabolic reprogramming in CD8+ T cells. Frontiers in Immunology, 13. 913184. ISSN 1664-3224
Abstract
T cell activation is dependent upon the integration of antigenic, co-stimulatory and cytokine-derived signals and the availability and acquisition of nutrients from the environment. Furthermore, T cell activation is accompanied by reprogramming of cellular metabolism to provide the energy and building blocks for proliferation, differentiation and effector function. Transforming growth factor β (TGFβ) has pleiotropic effects on T cell populations, having both an essential role in the maintenance of immune tolerance but also context-dependent pro-inflammatory functions. We set out to define the mechanisms underpinning the suppressive effects of TGFβ on mouse CD8+ T cell activation. RNA-sequencing analysis of TCR-stimulated T cells determined that Myc-regulated genes were highly enriched within gene sets downregulated by TGFβ. Functional analysis demonstrated that TGFβ impeded TCR-induced upregulation of amino acid transporter expression, amino acid uptake and protein synthesis. Furthermore, TCR-induced upregulation of Myc-dependent glycolytic metabolism was substantially inhibited by TGFβ treatment with minimal effects on mitochondrial respiration. Thus, our data suggest that inhibition of Myc-dependent metabolic reprogramming represents a major mechanism underpinning the suppressive effects of TGFβ on CD8+ T cell activation.
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Copyright, Publisher and Additional Information: | © 2022 Hope, Pickersgill, Ginefra, Vannini, Cook and Salmond. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). | ||||
Keywords: | T cells, T cell receptor, metabolism, cytokines, signalling, TGFb (transforming growth factor-beta) | ||||
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Institution: | The University of Leeds | ||||
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Depositing User: | Symplectic Publications | ||||
Date Deposited: | 18 Aug 2022 13:53 | ||||
Last Modified: | 18 Aug 2022 13:53 | ||||
Status: | Published | ||||
Publisher: | Frontiers Media | ||||
Identification Number: | https://doi.org/10.3389/fimmu.2022.913184 | ||||
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