Atypical cofilin signaling drives dendritic cell migration through the extracellular matrix via nuclear deformation

Harry Warner, Giulia Franciosa, Guus van der Borg, Britt Coenen, Felix Faas, Claire Koenig, Rinse de Boer, René Classens, Sjors Maassen, Maksim V Baranov, Shweta Mahajan, Deepti Dabral, Frans Bianchi, Niek van Hilten, Herre Jelger Risselada, Wouter H Roos, Jesper Velgaard Olsen, Laia Querol Cano, Geert van den Bogaart*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

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Samenvatting

To mount an adaptive immune response, dendritic cells must migrate to lymph nodes to present antigens to T cells. Critical to 3D migration is the nucleus, which is the size-limiting barrier for migration through the extracellular matrix. Here, we show that inflammatory activation of dendritic cells leads to the nucleus becoming spherically deformed and enables dendritic cells to overcome the typical 2- to 3-μm diameter limit for 3D migration through gaps in the extracellular matrix. We show that the nuclear shape change is partially attained through reduced cell adhesion, whereas improved 3D migration is achieved through reprogramming of the actin cytoskeleton. Specifically, our data point to a model whereby the phosphorylation of cofilin-1 at serine 41 drives the assembly of a cofilin-actomyosin ring proximal to the nucleus and enhances migration through 3D collagen gels. In summary, these data describe signaling events through which dendritic cells deform their nucleus and enhance their migratory capacity.

Originele taal-2English
Artikelnummer113866
Aantal pagina's28
TijdschriftCell reports
Volume43
Nummer van het tijdschrift3
Vroegere onlinedatum27-feb.-2024
DOI's
StatusPublished - 26-mrt.-2024

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