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

Author

Listed:
  • Diane Maurice

    (Francis Crick Institute
    Francis Crick Institute)

  • Patrick Costello

    (Francis Crick Institute)

  • Jessica Diring

    (Francis Crick Institute)

  • Francesco Gualdrini

    (Francis Crick Institute
    Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS))

  • Bruno Frederico

    (Francis Crick Institute
    AstraZeneca)

  • Richard Treisman

    (Francis Crick Institute)

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.

Suggested Citation

  • Diane Maurice & Patrick Costello & Jessica Diring & Francesco Gualdrini & Bruno Frederico & Richard Treisman, 2024. "IL-2 delivery to CD8+ T cells during infection requires MRTF/SRF-dependent gene expression and cytoskeletal dynamics," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52230-8
    DOI: 10.1038/s41467-024-52230-8
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    References listed on IDEAS

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    1. Matthew A. Williams & Aaron J. Tyznik & Michael J. Bevan, 2006. "Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells," Nature, Nature, vol. 441(7095), pages 890-893, June.
    2. Koichi Araki & Alexandra P. Turner & Virginia Oliva Shaffer & Shivaprakash Gangappa & Susanne A. Keller & Martin F. Bachmann & Christian P. Larsen & Rafi Ahmed, 2009. "mTOR regulates memory CD8 T-cell differentiation," Nature, Nature, vol. 460(7251), pages 108-112, July.
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