| Autor: |
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 |
| Zdroj: |
Cell Reports; March 2024, Vol. 43 Issue: 3 |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
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