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bioRxiv · 10.1101/2020.06.13.150045

Dendritic cell actin dynamics controls T cell priming efficiency at the immunological synapse

Leithner, A.·Altenburger, L. M.·Hauschild, R.·Assen, F.·Rottner, K.·Stradal, T. E. B.·Stein, J. V.·Sixt, M.
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Abstract

Dendritic cells (DCs) are crucial for the priming of naive T cells and the initiation of adaptive immunity. Priming is initiated at a heterologous cell-cell contact, the immunological synapse (IS). While it is established that actin dynamics regulates signalling at the T cell side of the contact, little is known about the cytoskeletal contribution on the DC side. We show that that the DC cytoskeleton is decisive for the formation of a multifocal synaptic structure, which correlates with T cell priming efficiency. We demonstrate that DC actin appears in transient foci at the IS and that these foci are dynamized by the WAVE complex. Absence of WAVE in DCs leads to stabilized contacts with T cells, caused by an increase in ICAM1-integrin mediated cell-cell adhesions. This results in a lower number of activated and proliferating T cells. Our results reveal an important role of DC actin in the regulation of synaptic contacts with crucial relevance for full T cell expansion.

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Leithner, A., Altenburger, L. M., Hauschild, R., Assen, F., Rottner, K., Stradal, T. E. B., Stein, J. V., Sixt, M.. 2020-06-14. Dendritic cell actin dynamics controls T cell priming efficiency at the immunological synapse. https://doi.org/10.1101/2020.06.13.150045

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