Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.
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Authors
Kishore, Madhav
Cheung, Kenneth CP
Fu, Hongmei
Bonacina, Fabrizia
Wang, Guosu
Coe, David
Ward, Eleanor J
Colamatteo, Alessandra
Jangani, Maryam
Baragetti, Andrea
Matarese, Giuseppe
Smith, David M
Haas, Robert
Mauro, Claudio
Wraith, David C
Catapano, Alberico L
De Rosa, Veronica
Norata, Giuseppe D
Marelli-Berg, Federica M
Publication Date
2017-11-21Journal Title
Immunity
ISSN
1074-7613
Publisher
Elsevier BV
Volume
47
Issue
5
Pages
875-889.e10
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print
Metadata
Show full item recordCitation
Kishore, M., Cheung, K. C., Fu, H., Bonacina, F., Wang, G., Coe, D., Ward, E. J., et al. (2017). Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.. Immunity, 47 (5), 875-889.e10. https://doi.org/10.1016/j.immuni.2017.10.017
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.
Keywords
Cells, Cultured, Animals, Mice, Inbred Strains, Humans, Mice, Glucokinase, Adaptor Proteins, Signal Transducing, Glycolysis, T-Lymphocytes, Regulatory, Proto-Oncogene Proteins c-akt, Phosphatidylinositol 3-Kinases, CTLA-4 Antigen, Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, CD28 Antigens
Identifiers
External DOI: https://doi.org/10.1016/j.immuni.2017.10.017
This record's URL: https://www.repository.cam.ac.uk/handle/1810/271041
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: http://creativecommons.org/licenses/by-nc-nd/4.0/
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