Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis

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Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis. / Kishore, Madhav; Cheung, Kenneth C P; 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; Okkenhaug, Klaus; Catapano, Alberico L; De Rosa, Veronica; Norata, Giuseppe D; Marelli-Berg, Federica M.

In: Immunity, Vol. 47, No. 5, 21.11.2017, p. 875-889.e10.

Research output: Contribution to journalArticle

Harvard

Kishore, M, Cheung, KCP, Fu, H, Bonacina, F, Wang, G, Coe, D, Ward, EJ, Colamatteo, A, Jangani, M, Baragetti, A, Matarese, G, Smith, DM, Haas, R, Mauro, C, Wraith, D, Okkenhaug, K, Catapano, AL, De Rosa, V, Norata, GD & Marelli-Berg, FM 2017, 'Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis', Immunity, vol. 47, no. 5, pp. 875-889.e10. https://doi.org/10.1016/j.immuni.2017.10.017

APA

Kishore, M., Cheung, K. C. P., Fu, H., Bonacina, F., Wang, G., Coe, D., Ward, E. J., Colamatteo, A., Jangani, M., Baragetti, A., Matarese, G., Smith, D. M., Haas, R., Mauro, C., Wraith, D., Okkenhaug, K., Catapano, A. L., De Rosa, V., Norata, G. D., & Marelli-Berg, F. M. (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

Vancouver

Kishore M, Cheung KCP, Fu H, Bonacina F, Wang G, Coe D et al. Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis. Immunity. 2017 Nov 21;47(5):875-889.e10. https://doi.org/10.1016/j.immuni.2017.10.017

Author

Kishore, Madhav ; Cheung, Kenneth C P ; 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 ; Okkenhaug, Klaus ; Catapano, Alberico L ; De Rosa, Veronica ; Norata, Giuseppe D ; Marelli-Berg, Federica M. / Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis. In: Immunity. 2017 ; Vol. 47, No. 5. pp. 875-889.e10.

Bibtex

@article{df93d380517c43e091a40c839d33e269,
title = "Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis",
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 = "regulatory T cells, metabolism, migration, glycolysis, mTOR, CD28, CTLA-4",
author = "Madhav Kishore and Cheung, {Kenneth C P} and Hongmei Fu and Fabrizia Bonacina and Guosu Wang and David Coe and Ward, {Eleanor J} and Alessandra Colamatteo and Maryam Jangani and Andrea Baragetti and Giuseppe Matarese and Smith, {David M} and Robert Haas and Claudio Mauro and David Wraith and Klaus Okkenhaug and Catapano, {Alberico L} and {De Rosa}, Veronica and Norata, {Giuseppe D} and Marelli-Berg, {Federica M}",
note = "Copyright {\textcopyright} 2017 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = nov,
day = "21",
doi = "10.1016/j.immuni.2017.10.017",
language = "English",
volume = "47",
pages = "875--889.e10",
journal = "Immunity",
issn = "1074-7613",
publisher = "Elsevier",
number = "5",

}

RIS

TY - JOUR

T1 - Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis

AU - Kishore, Madhav

AU - Cheung, Kenneth C P

AU - Fu, Hongmei

AU - Bonacina, Fabrizia

AU - Wang, Guosu

AU - Coe, David

AU - Ward, Eleanor J

AU - Colamatteo, Alessandra

AU - Jangani, Maryam

AU - Baragetti, Andrea

AU - Matarese, Giuseppe

AU - Smith, David M

AU - Haas, Robert

AU - Mauro, Claudio

AU - Wraith, David

AU - Okkenhaug, Klaus

AU - Catapano, Alberico L

AU - De Rosa, Veronica

AU - Norata, Giuseppe D

AU - Marelli-Berg, Federica M

N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2017/11/21

Y1 - 2017/11/21

N2 - 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.

AB - 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.

KW - regulatory T cells

KW - metabolism

KW - migration

KW - glycolysis

KW - mTOR

KW - CD28

KW - CTLA-4

U2 - 10.1016/j.immuni.2017.10.017

DO - 10.1016/j.immuni.2017.10.017

M3 - Article

C2 - 29166588

VL - 47

SP - 875-889.e10

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 5

ER -