Year: 2017
Type: article
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.
Source: Immunity
Authors: Madhav Kishore, Kenneth C.P. Cheung, Hongmei Fu, Fabrizia Bonacina, Guosu Wang, David Coe, Eleanor J. Ward, Alessandra Colamatteo, Maryam Jangani, Andrea Baragetti, Giuseppe Matarese, David M. Smith, Robert Haas, Claudio Mauro, David C. Wraith, Klaus Okkenhaug, Alberico L. Catapano, Veronica De Rosa, Giuseppe D. Norata, Federica M. Marelli-Berg
Institutions: Queen Mary University of London, William Harvey Research Institute, University of Milan, Institute for Experimental Endocrinology and Oncology, National Research Council, University of Naples Federico II, AstraZeneca (United Kingdom), University of Birmingham, Babraham Institute, MultiMedica, Curtin University
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Awards: Immune responses to the environment, Lymphocyte development & homeostasis., G342161892, Investigating the metabolic control of T cell migration: implications for immune inflammation in physiology and cardiovascular metabolic disease, G4956830957, How bioactive lipid mediators control T cell migration: basic mechanisms and therapeutic potential for cardiovascular metabolic disorders, Centre for Musculoskeletal Ageing Research, Develop a mechanistic understanding of how transcriptional and posttranscriptional regulation of gene expression is coordinated by signal transduction pathways., G5983213847, G6126724757, Investigating the topography of effector and regulatory immunity in the cardiovascular system: basic mechanisms and therapeutic potential (renewal), Immune homeostasis and the immune response, G7482630759, The BHF Chair of Cardiovascular Immunology, Molecular mechanisms of endothelial cytoprotection by CD31-mediated signals
OpenAlex ID: W2769148407