Arp2/3 complex-dependent actin regulation protects the survival of tissue-resident mast cells

Kaltenbach, L.; Mihlan, M.; Ulferts, S.; Müsken, M.; Glaser, K. M.; Mittler, G.; Babina, M.; Innocenti, M.; Grosse, R.; Stradal, T. E. B.; Lämmermann, T.

doi:10.1101/2024.02.23.581763

bioRxiv · 10.1101/2024.02.23.581763

Arp2/3 complex-dependent actin regulation protects the survival of tissue-resident mast cells

Kaltenbach, L.·Mihlan, M.·Ulferts, S.·Müsken, M.·Glaser, K. M.·Mittler, G.·Babina, M.·Innocenti, M.·Grosse, R.·Stradal, T. E. B.·Lämmermann, T.

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Abstract

Actin network dynamics are pivotal in governing the motility and effector functions of immune cells. The Arp2/3 complex is a key regulator of actin filament branching, with mutations in its subunits being linked with human immunodeficiencies. While known for its role in phagocytosis and cell migration, our study uncovers a critical role of the Arp2/3 complex in safeguarding the tissue residency of mast cells (MCs), essential immune cells in allergies, venom detoxification and antigen-specific avoidance. Mechanistically, we show that MCs require Arp2/3-regulated actin filament assembly to resist their integrin-mediated mechano-coupling with their tissue niche. Arp2/3 complex depletion directs MCs into cell cycle arrest and death, which can be rescued by inhibiting their mechanical interactions with extracellular matrix. Our findings underscore the Arp2/3 complex as a mechano-protective element for maintaining MC survival and longevity in tissues, highlighting the importance of actin regulation in preserving the homeostasis of a tissue-resident immune cell population. One Sentence SummaryArp2/3 complex protects the tissue homeostasis of resident mast cell networks

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Kaltenbach, L., Mihlan, M., Ulferts, S., Müsken, M., Glaser, K. M., Mittler, G., Babina, M., Innocenti, M., Grosse, R., Stradal, T. E. B., Lämmermann, T.. 2024-02-25. Arp2/3 complex-dependent actin regulation protects the survival of tissue-resident mast cells. https://doi.org/10.1101/2024.02.23.581763

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