Abstract

The ability to proliferate is a common feature of most T-cell populations. However, proliferation follows different cell-cycle dynamics and is coupled to different functional outcomes according to T-cell subsets. Whether the mitotic machineries supporting these qualitatively distinct proliferative responses are identical remains unknown. Here, we show that disruption of the microtubule-associated protein LIS1 in mouse models leads to proliferative defects associated with a blockade of T-cell development after b-selection and of peripheral CD4+ T cell expansion after antigen priming. In contrast, cell divisions in CD8+ T cells occurred independently of LIS1 following T-cell antigen receptor stimulation, although LIS1 was required for proliferation elicited by pharmacological activation. In thymocytes and CD4+ T cells, LIS1-deficiency did not affect signaling events leading to activation but led to an interruption of proliferation after the initial round of division and to p53-induced cell death. Proliferative defects resulted from a mitotic failure, characterized by the presence of extra-centrosomes and the formation of multipolar spindles, causing abnormal chromosomes congression during metaphase and separation during telophase. LIS1 was required to stabilize dynein/dynactin complexes, which promote chromosome attachment to mitotic spindles and ensure centrosome integrity. Together, these results suggest that proliferative responses are supported by distinct mitotic machineries across T-cell subsets.

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All data generated or analysed during this study are included in the manuscript and supporting file have been provided for Figures 1 and 3.

Article and author information

Author details

  1. Jérémy Argenty

    Toulouse Institute for Infectious and Inflammatory Diseases, Inserm, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Nelly Rouquié

    Toulouse Institute for Infectious and Inflammatory Diseases, Inserm, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Cyrielle Bories

    Toulouse Institute for Infectious and Inflammatory Diseases, Inserm, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Suzanne Mélique

    Toulouse Institute for Infectious and Inflammatory Diseases, Inserm, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Valérie Duplan-Eche

    Toulouse Institute for Infectious and Inflammatory Diseases, Inserm, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Abdelhadi Saoudi

    Toulouse Institute for Infectious and Inflammatory Diseases, Inserm, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7015-8178
  7. Nicolas Fazilleau

    Toulouse Institute for Infectious and Inflammatory Diseases, Inserm, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Renaud Lesourne

    Toulouse Institute for Infectious and Inflammatory Diseases, Inserm, Toulouse, France
    For correspondence
    renaud.lesourne@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3816-7087

Funding

The French ministry of higher education and reserach (PhD fellowship)

  • Jérémy Argenty
  • Suzanne Mélique

Association pour la recherche sur la Sclérose en Plaques

  • Renaud Lesourne

Agence Nationale de la Recherche (ANR-20-CE15-0002)

  • Renaud Lesourne

Association pour la Recherche sur le Cancer

  • Renaud Lesourne

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Sarah Russell, Peter MacCallum Cancer Centre, Australia

Ethics

Animal experimentation: All the experiments were conducted at the INSERM animal facility (US-006; accreditation number A-31 55508 delivered by the French Ministry of Agriculture to perform experiments on live mice). All experimental protocols were approved by a Ministry-approved ethics committee (CEEA-122) and follow the French and European regulations on care and protection of the Laboratory Animals (EC Directive 2010/63).

Version history

  1. Received: May 13, 2022
  2. Preprint posted: May 25, 2022 (view preprint)
  3. Accepted: December 11, 2022
  4. Accepted Manuscript published: December 15, 2022 (version 1)
  5. Version of Record published: December 28, 2022 (version 2)

Copyright

© 2022, Argenty et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jérémy Argenty
  2. Nelly Rouquié
  3. Cyrielle Bories
  4. Suzanne Mélique
  5. Valérie Duplan-Eche
  6. Abdelhadi Saoudi
  7. Nicolas Fazilleau
  8. Renaud Lesourne
(2022)
A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage
eLife 11:e80277.
https://doi.org/10.7554/eLife.80277

Share this article

https://doi.org/10.7554/eLife.80277

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