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

Medical University of Vienna. Department of Dermatology. Vienna, Austria / Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases. Vienna, Austria.
Medical University of Vienna. Department of Dermatology. Vienna, Austria / Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases. Vienna, Austria.
Medical University of Vienna. Department of Dermatology. Vienna, Austria.
Toulouse III Paul Sabatier University. Institut National de la Santé et de la Recherche Médicale. Centre National de la Recherche Scientifique. Toulouse Institute for Infectious and Inflammatory Diseases. Toulouse, France / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Fiocruz Ceará. Eusébio, CE, Brasil.
Toulouse III Paul Sabatier University. Institut National de la Santé et de la Recherche Médicale. Centre National de la Recherche Scientifique. Toulouse Institute for Infectious and Inflammatory Diseases. Toulouse, France.
Medical University of Vienna. Department of Dermatology. Vienna, Austria.
Medical University of Vienna. Department of Dermatology. Vienna, Austria.
Austrian Academy of Sciences. Research Center for Molecular Medicine. Vienna, Austria.
Austrian Academy of Sciences. Research Center for Molecular Medicine. Vienna, Austria / University of Vienna. Max Perutz Labs. Vienna, Austria.
Medical University of Vienna. Department of Dermatology. Vienna, Austria.
Medical University of Vienna. Department of Dermatology. Vienna, Austria.
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases. Vienna, Austria / Austrian Academy of Sciences. Research Center for Molecular Medicine. Vienna, Austria / St. Anna Children's Cancer Research Institute. Vienna, Austria / Medical University of Vienna. Department of Pediatrics and Adolescent Medicine. Vienna, Austria.
Medical University of Vienna. Department of Dermatology. Vienna, Austria / Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases. Vienna, Austria / Toulouse III Paul Sabatier University. Institut National de la Santé et de la Recherche Médicale. Centre National de la Recherche Scientifique. Toulouse Institute for Infectious and Inflammatory Diseases. Toulouse, France.

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.

Keywords

Cytotoxic T cells
Adhesion
Motility
Immunological synapse
Actin cytoskeleton
ARP2/3 complex
IL-2
Glycolysis
OXPHOS
High-content cell imaging
RNA sequencing

Publisher

Cell Press

Citation

KAMNEV, Anton et al. Coordinated ARP2/3 and glycolytic activities regulate the morphological and functional fitness of human CD8⁺ T cells. Cell Reports, v. 43, n. 3, p. 1-33, 29 Feb. 2024.

DOI

10.1016/j.celrep.2024.113853

ISSN

2639-1856

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/63475

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Copyright

Open access

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