Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation

Kristen N. Pollizzi, Im Hong Sun, Chirag H. Patel, Ying Chun Lo, Min Hee Oh, Adam T. Waickman, Ada J. Tam, Richard L. Blosser, Jiayu Wen, Greg M. Delgoffe, Jonathan Powell

Research output: Contribution to journalArticle

Abstract

The asymmetric partitioning of fate-determining proteins has been shown to contribute to the generation of CD8+ effector and memory T cell precursors. Here we demonstrate the asymmetric partitioning of mTORC1 activity after the activation of naive CD8+ T cells. This results in the generation of two daughter T cells, one of which shows increased mTORC1 activity, increased glycolytic activity and increased expression of effector molecules. The other daughter T cell has relatively low mTORC1 activity and increased lipid metabolism, expresses increased amounts of anti-apoptotic molecules and subsequently displays enhanced long-term survival. Mechanistically, we demonstrate a link between T cell antigen receptor (TCR)-induced asymmetric expression of amino acid transporters and RagC-mediated translocation of mTOR to the lysosomes. Overall, our data provide important insight into how mTORC1-mediated metabolic reprogramming affects the fate decisions of T cells.

Original languageEnglish (US)
JournalNature Immunology
DOIs
StateAccepted/In press - Apr 11 2016

Fingerprint

Cell Differentiation
Phosphotransferases
T-Lymphocytes
T-Lymphoid Precursor Cells
Amino Acid Transport Systems
T-Cell Antigen Receptor
Lysosomes
Lipid Metabolism
mechanistic target of rapamycin complex 1
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation. / Pollizzi, Kristen N.; Sun, Im Hong; Patel, Chirag H.; Lo, Ying Chun; Oh, Min Hee; Waickman, Adam T.; Tam, Ada J.; Blosser, Richard L.; Wen, Jiayu; Delgoffe, Greg M.; Powell, Jonathan.

In: Nature Immunology, 11.04.2016.

Research output: Contribution to journalArticle

Pollizzi, KN, Sun, IH, Patel, CH, Lo, YC, Oh, MH, Waickman, AT, Tam, AJ, Blosser, RL, Wen, J, Delgoffe, GM & Powell, J 2016, 'Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation', Nature Immunology. https://doi.org/10.1038/ni.3438
Pollizzi, Kristen N. ; Sun, Im Hong ; Patel, Chirag H. ; Lo, Ying Chun ; Oh, Min Hee ; Waickman, Adam T. ; Tam, Ada J. ; Blosser, Richard L. ; Wen, Jiayu ; Delgoffe, Greg M. ; Powell, Jonathan. / Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation. In: Nature Immunology. 2016.
@article{735bf337251c41b88c88de5128817f31,
title = "Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation",
abstract = "The asymmetric partitioning of fate-determining proteins has been shown to contribute to the generation of CD8+ effector and memory T cell precursors. Here we demonstrate the asymmetric partitioning of mTORC1 activity after the activation of naive CD8+ T cells. This results in the generation of two daughter T cells, one of which shows increased mTORC1 activity, increased glycolytic activity and increased expression of effector molecules. The other daughter T cell has relatively low mTORC1 activity and increased lipid metabolism, expresses increased amounts of anti-apoptotic molecules and subsequently displays enhanced long-term survival. Mechanistically, we demonstrate a link between T cell antigen receptor (TCR)-induced asymmetric expression of amino acid transporters and RagC-mediated translocation of mTOR to the lysosomes. Overall, our data provide important insight into how mTORC1-mediated metabolic reprogramming affects the fate decisions of T cells.",
author = "Pollizzi, {Kristen N.} and Sun, {Im Hong} and Patel, {Chirag H.} and Lo, {Ying Chun} and Oh, {Min Hee} and Waickman, {Adam T.} and Tam, {Ada J.} and Blosser, {Richard L.} and Jiayu Wen and Delgoffe, {Greg M.} and Jonathan Powell",
year = "2016",
month = "4",
day = "11",
doi = "10.1038/ni.3438",
language = "English (US)",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation

AU - Pollizzi, Kristen N.

AU - Sun, Im Hong

AU - Patel, Chirag H.

AU - Lo, Ying Chun

AU - Oh, Min Hee

AU - Waickman, Adam T.

AU - Tam, Ada J.

AU - Blosser, Richard L.

AU - Wen, Jiayu

AU - Delgoffe, Greg M.

AU - Powell, Jonathan

PY - 2016/4/11

Y1 - 2016/4/11

N2 - The asymmetric partitioning of fate-determining proteins has been shown to contribute to the generation of CD8+ effector and memory T cell precursors. Here we demonstrate the asymmetric partitioning of mTORC1 activity after the activation of naive CD8+ T cells. This results in the generation of two daughter T cells, one of which shows increased mTORC1 activity, increased glycolytic activity and increased expression of effector molecules. The other daughter T cell has relatively low mTORC1 activity and increased lipid metabolism, expresses increased amounts of anti-apoptotic molecules and subsequently displays enhanced long-term survival. Mechanistically, we demonstrate a link between T cell antigen receptor (TCR)-induced asymmetric expression of amino acid transporters and RagC-mediated translocation of mTOR to the lysosomes. Overall, our data provide important insight into how mTORC1-mediated metabolic reprogramming affects the fate decisions of T cells.

AB - The asymmetric partitioning of fate-determining proteins has been shown to contribute to the generation of CD8+ effector and memory T cell precursors. Here we demonstrate the asymmetric partitioning of mTORC1 activity after the activation of naive CD8+ T cells. This results in the generation of two daughter T cells, one of which shows increased mTORC1 activity, increased glycolytic activity and increased expression of effector molecules. The other daughter T cell has relatively low mTORC1 activity and increased lipid metabolism, expresses increased amounts of anti-apoptotic molecules and subsequently displays enhanced long-term survival. Mechanistically, we demonstrate a link between T cell antigen receptor (TCR)-induced asymmetric expression of amino acid transporters and RagC-mediated translocation of mTOR to the lysosomes. Overall, our data provide important insight into how mTORC1-mediated metabolic reprogramming affects the fate decisions of T cells.

UR - http://www.scopus.com/inward/record.url?scp=84963525930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963525930&partnerID=8YFLogxK

U2 - 10.1038/ni.3438

DO - 10.1038/ni.3438

M3 - Article

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

ER -