IL-2 delivery to CD8+ T cells during infection requires MRTF/SRF-dependent gene expression and cytoskeletal dynamics

Diane Maurice, Patrick Costello, Jessica Diring, Francesco Gualdrini, Bruno Frederico and Richard Treisman ()
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Diane Maurice: Francis Crick Institute
Patrick Costello: Francis Crick Institute
Jessica Diring: Francis Crick Institute
Francesco Gualdrini: Francis Crick Institute
Bruno Frederico: Francis Crick Institute
Richard Treisman: Francis Crick Institute

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract Paracrine IL-2 signalling drives the CD8 + T cell expansion and differentiation that allow protection against viral infections, but the underlying molecular events are incompletely understood. Here we show that the transcription factor SRF, a master regulator of cytoskeletal gene expression, is required for effective IL-2 signalling during L. monocytogenes infection. Acting cell-autonomously with its actin-regulated cofactors MRTF-A and MRTF-B, SRF is dispensible for initial TCR-mediated CD8+ T cell proliferation, but is required for sustained IL-2 dependent CD8+ effector T cell expansion, and persistence of memory cells. Following TCR activation, Mrtfab-null CD8+ T cells produce IL-2 normally, but homotypic clustering is impaired both in vitro and in vivo. Expression of cytoskeletal structural and regulatory genes, most notably actins, is defective in Mrtfab-null CD8+ T cells. Activation-induced cell clustering in vitro requires F-actin assembly, and Mrtfab-null cell clusters are small, contain less F-actin, and defective in IL-2 retention. Clustering of Mrtfab-null cells can be partially restored by exogenous actin expression. IL-2 mediated CD8+ T cell proliferation during infection thus depends on the control of cytoskeletal dynamics and actin gene expression by MRTF-SRF signalling.

Date: 2024
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DOI: 10.1038/s41467-024-52230-8

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