Kishore, M;
Cheung, KCP;
Fu, H;
Bonacina, F;
Wang, G;
Coe, D;
Ward, EJ;
... Marelli-Berg, FM; + view all
(2017)
Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.
Immunity
, 47
(5)
875-889.e10.
10.1016/j.immuni.2017.10.017.
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Abstract
Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK). Subsequently, GCK promoted cytoskeletal rearrangements by associating with actin. Treg cells lacking this pathway were functionally suppressive but failed to migrate to skin allografts and inhibit rejection. Similarly, human carriers of a loss-of-function GCK regulatory protein gene—leading to increased GCK activity—had reduced numbers of circulating Treg cells. These cells displayed enhanced migratory activity but similar suppressive function, while conventional T cells were unaffected. Thus, GCK-dependent glycolysis regulates Treg cell migration.
| Type: | Article |
|---|---|
| Title: | Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.immuni.2017.10.017 |
| Publisher version: | https://doi.org/10.1016/j.immuni.2017.10.017 |
| Language: | English |
| Additional information: | Copyright © 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | regulatory T cells, metabolism, migration, glycolysis, mTOR, CD28, CTLA-4 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10046974 |
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