Coordinated ARP2/3 and glycolytic activities regulate the morphological and functional fitness of human CD8 T cells.

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ID: 278382
2024
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Abstract
Actin cytoskeleton remodeling sustains the ability of cytotoxic T cells to search for target cells and eliminate them. We here investigated the relationship between energetic status, actin remodeling, and functional fitness in human CD8 effector T cells. Cell spreading during migration or immunological synapse assembly mirrored cytotoxic activity. Morphological and functional fitness were boosted by interleukin-2 (IL-2), which also stimulated the transcription of glycolytic enzymes, actin isoforms, and actin-related protein (ARP)2/3 complex subunits. This molecular program scaled with F-actin content and cell spreading. Inhibiting glycolysis impaired F-actin remodeling at the lamellipodium, chemokine-driven motility, and adhesion, while mitochondrial oxidative phosphorylation blockade impacted cell elongation during confined migration. The severe morphological and functional defects of ARPC1B-deficient T cells were only partially corrected by IL-2, emphasizing ARP2/3-mediated actin polymerization as a crucial energy state integrator. The study therefore underscores the tight coordination between metabolic and actin remodeling programs to sustain the cytotoxic activity of CD8 T cells.
Reference Key
kamnev2024coordinatedcell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Kamnev, Anton;Mehta, Tanvi;Wielscher, Matthias;Chaves, Beatriz;Lacouture, Claire;Mautner, Anna-Katharina;Shaw, Lisa E;Caldera, Michael;Menche, Jörg;Weninger, Wolfgang P;Farlik, Matthias;Boztug, Kaan;Dupré, Loïc;
Journal Cell reports
Year 2024
DOI
10.1016/j.celrep.2024.113853
URL
Keywords
adhesion actin cytoskeleton rna sequencing motility il-2 oxphos glycolysis arp2/3 complex cp: cell biology cp: immunology cytotoxic t cells high-content cell imaging immunological synapse

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