Antigen receptor control of amino acid transport coordinates the metabolic re-programming that is essential for T cell differentiation

T lymphocytes regulate nutrient uptake to meet the metabolic demands of immune activation. The present study shows that the intracellular supply of large neutral amino acids (LNAAs) in T cells is regulated by pathogen and the T cell antigen receptor (TCR). A single System L transporter, Slc7a5, medi...

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Autores principales: Sinclair, Linda V., Rolf, Julia, Emslie, Elizabeth, Shi, Yun-Bo, Taylor, Peter M., Cantrell, Doreen A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672957/
https://www.ncbi.nlm.nih.gov/pubmed/23525088
http://dx.doi.org/10.1038/ni.2556
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author Sinclair, Linda V.
Rolf, Julia
Emslie, Elizabeth
Shi, Yun-Bo
Taylor, Peter M.
Cantrell, Doreen A.
author_facet Sinclair, Linda V.
Rolf, Julia
Emslie, Elizabeth
Shi, Yun-Bo
Taylor, Peter M.
Cantrell, Doreen A.
author_sort Sinclair, Linda V.
collection PubMed
description T lymphocytes regulate nutrient uptake to meet the metabolic demands of immune activation. The present study shows that the intracellular supply of large neutral amino acids (LNAAs) in T cells is regulated by pathogen and the T cell antigen receptor (TCR). A single System L transporter, Slc7a5, mediated LNAA uptake in activated T cells. Slc7a5-null T cells could not metabolically reprogram in response to antigen and failed clonal expansion and effector differentiation. The metabolic catastrophe caused by Slc7a5 loss reflects the requirement for sustained uptake of the LNAA leucine for activation of mammalian target of rapamycin complex 1 (mTORC1) and for expression of c-myc. Pathogen control of System L transporters is thus a critical metabolic checkpoint for T cells.
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spelling pubmed-36729572013-11-01 Antigen receptor control of amino acid transport coordinates the metabolic re-programming that is essential for T cell differentiation Sinclair, Linda V. Rolf, Julia Emslie, Elizabeth Shi, Yun-Bo Taylor, Peter M. Cantrell, Doreen A. Nat Immunol Article T lymphocytes regulate nutrient uptake to meet the metabolic demands of immune activation. The present study shows that the intracellular supply of large neutral amino acids (LNAAs) in T cells is regulated by pathogen and the T cell antigen receptor (TCR). A single System L transporter, Slc7a5, mediated LNAA uptake in activated T cells. Slc7a5-null T cells could not metabolically reprogram in response to antigen and failed clonal expansion and effector differentiation. The metabolic catastrophe caused by Slc7a5 loss reflects the requirement for sustained uptake of the LNAA leucine for activation of mammalian target of rapamycin complex 1 (mTORC1) and for expression of c-myc. Pathogen control of System L transporters is thus a critical metabolic checkpoint for T cells. 2013-03-24 2013-05 /pmc/articles/PMC3672957/ /pubmed/23525088 http://dx.doi.org/10.1038/ni.2556 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Sinclair, Linda V.
Rolf, Julia
Emslie, Elizabeth
Shi, Yun-Bo
Taylor, Peter M.
Cantrell, Doreen A.
Antigen receptor control of amino acid transport coordinates the metabolic re-programming that is essential for T cell differentiation
title Antigen receptor control of amino acid transport coordinates the metabolic re-programming that is essential for T cell differentiation
title_full Antigen receptor control of amino acid transport coordinates the metabolic re-programming that is essential for T cell differentiation
title_fullStr Antigen receptor control of amino acid transport coordinates the metabolic re-programming that is essential for T cell differentiation
title_full_unstemmed Antigen receptor control of amino acid transport coordinates the metabolic re-programming that is essential for T cell differentiation
title_short Antigen receptor control of amino acid transport coordinates the metabolic re-programming that is essential for T cell differentiation
title_sort antigen receptor control of amino acid transport coordinates the metabolic re-programming that is essential for t cell differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672957/
https://www.ncbi.nlm.nih.gov/pubmed/23525088
http://dx.doi.org/10.1038/ni.2556
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