The Arp2/3 complex maintains genome integrity and survival of epidermal Langerhans cells
Myeloid cells use intracellular actin networks for key cellular processes, including cell migration and chemotaxis, phagocytosis or macropinocytosis, as well as immune synapse formation. However, whether actin networks play any role in the development and/or survival of myeloid cells in tissues remains open. Here, we find that the Arp2/3 complex, which is responsible for the nucleation of branched actin networks, is needed for in vivo maintenance of epidermal Langerhans cells (LCs) throughout life. Mice harboring a genetic deletion of the Arpc4 subunit of the complex in myeloid cells form LC networks at birth, but these cells decline in numbers following a process reminiscent of premature cellular aging. By combining in vivo analyses of LCs with in vitro experiments on bone-marrow-derived dendritic cells, we find that Arpc4-deficient cells manage to progress through the cell cycle but accumulate DNA damage associated with aberrant nuclear shapes, lamina reduction and events of nuclear envelope rupture. These results provide evidence for a physiological role of Arp2/3 in maintenance of genome integrity and survival of immune cells in tissues.
Authors
- Daniele Fachinetti (ORCID: https://orcid.org/0000-0002-8795-6771)
- Sandra Iden (ORCID: https://orcid.org/0000-0003-2333-9827)
- Zahraa Alraies (ORCID: https://orcid.org/0000-0002-1277-1625)
- Vincent Calmettes (ORCID: https://orcid.org/0000-0001-6943-9116)
- Doriane Sanséau (ORCID: https://orcid.org/0000-0002-9427-2458)
- Lívia Lacerda Mariano (ORCID: https://orcid.org/0000-0002-2749-4878)
- Roberto Amadio (ORCID: https://orcid.org/0000-0003-0861-0703)
- Florent Ginhoux (ORCID: https://orcid.org/0000-0002-2857-7755)
- Mathieu Maurin (ORCID: https://orcid.org/0000-0003-3555-6247)
- Nilushi De Silva (ORCID: https://orcid.org/0009-0003-1156-7010)
- Aurélien Dauphin (ORCID: https://orcid.org/0000-0001-9744-8458)
- Charlotte Canet-Jourdan (ORCID: https://orcid.org/0000-0001-7310-2620)
- Anna Chipont (ORCID: https://orcid.org/0000-0002-3711-404X)
- Anna Shmakova (ORCID: https://orcid.org/0000-0001-7162-074X)
- Ann-Kathrin Burkhart (ORCID: https://orcid.org/0000-0003-4128-6677)
- Coralie L. Guérin (ORCID: https://orcid.org/0000-0002-1840-4017)
- Federica Benvenuti (ORCID: https://orcid.org/0000-0002-1908-8052)
- Nicolas Manel (ORCID: https://orcid.org/0000-0002-1481-4430)
- Javiera Villar (ORCID: https://orcid.org/0000-0002-8581-4155)
- Ana‐Maria Lennon‐Duménil (ORCID: https://orcid.org/0000-0003-4383-1034)
- Maria–Graciela Delgado (ORCID: https://orcid.org/0000-0001-7890-0728)
- Vanessa Samira Rácz (ORCID: https://orcid.org/0009-0007-4884-1051)
- Mabel San Roman
- Giulia Bracchetti
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Paris Sciences et Lettres (FR)
- Institut Gustave Roussy (FR)
- Sorbonne Université (FR)
- Dynamique du noyau (FR)
- Biologie cellulaire et Cancer (FR)
- Génétique et biologie du développement (FR)
- Institut Curie (FR)
- International Centre for Genetic Engineering and Biotechnology (IT)
- Saarland University (DE)
Publication Details
- Journal
- EMBO Reports
- Published
- 2026-11-07
- DOI
- https://doi.org/10.1038/s44319-026-00982-3
- Citations
- 3
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 1.87
Funders
- Infrastructures en Biologie Santé et Agronomie
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Fondation ARC pour la Recherche sur le Cancer
- Universität des Saarlandes
- Institut National Du Cancer
- European Research Council