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 F-actin dynamics regulates signaling at the T cell side of the contact, little is known about the cytoskeletal contribution on the DC side. Here, we show that the DC actin cytoskeleton is decisive for the formation of a multifocal synaptic structure, which correlates with T cell priming efficiency. DC actin at the IS appears in transient foci that are dynamized by the WAVE regulatory complex (WRC). The absence of the WRC in DCs leads to stabilized contacts with T cells, caused by an increase in ICAM1-integrin–mediated cell–cell adhesion. This results in lower numbers of activated and proliferating T cells, demonstrating an important role for DC actin in the regulation of immune synapse functionality.
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February 03 2021
Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse
Alexander Leithner
,
1
Institute of Science and Technology Austria, Klosterneuburg, Austria
6Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
Correspondence to Alexander Leithner: alexander.leithner@ist.ac.at
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Lukas M. Altenburger
,
Lukas M. Altenburger
2
Department of Oncology, Microbiology and Immunology, University of Fribourg, Fribourg, Switzerland
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Robert Hauschild
,
Robert Hauschild
1
Institute of Science and Technology Austria, Klosterneuburg, Austria
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Frank P. Assen
,
Frank P. Assen
1
Institute of Science and Technology Austria, Klosterneuburg, Austria
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Klemens Rottner
,
Klemens Rottner
3
Zoological Institute, Technical University Braunschweig, Braunschweig, Germany
4
Department of Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
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Theresia E.B. Stradal
,
Theresia E.B. Stradal
4
Department of Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
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Alba Diz-Muñoz
,
Alba Diz-Muñoz
5
Cell Biology and Biophysics Units, European Molecular Biology Laboratory, Heidelberg, Germany
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Jens V. Stein
,
Jens V. Stein
2
Department of Oncology, Microbiology and Immunology, University of Fribourg, Fribourg, Switzerland
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Michael Sixt
1
Institute of Science and Technology Austria, Klosterneuburg, Austria
Michael Sixt: michael.sixt@ist.ac.at
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Alexander Leithner
1
Institute of Science and Technology Austria, Klosterneuburg, Austria
6Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
Lukas M. Altenburger
2
Department of Oncology, Microbiology and Immunology, University of Fribourg, Fribourg, Switzerland
Robert Hauschild
1
Institute of Science and Technology Austria, Klosterneuburg, Austria
Frank P. Assen
1
Institute of Science and Technology Austria, Klosterneuburg, Austria
Klemens Rottner
3
Zoological Institute, Technical University Braunschweig, Braunschweig, Germany
4
Department of Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
Theresia E.B. Stradal
4
Department of Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
Alba Diz-Muñoz
5
Cell Biology and Biophysics Units, European Molecular Biology Laboratory, Heidelberg, Germany
Jens V. Stein
2
Department of Oncology, Microbiology and Immunology, University of Fribourg, Fribourg, Switzerland
Michael Sixt
1
Institute of Science and Technology Austria, Klosterneuburg, Austria
Correspondence to Alexander Leithner: alexander.leithner@ist.ac.at
Michael Sixt: michael.sixt@ist.ac.at
Received:
June 13 2020
Revision Received:
November 25 2020
Accepted:
January 12 2021
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding:
Austrian Science Fund
(FWF P29911)
Deutsche Forschungsgemeinschaft
(PROCOMPAS GRK2223/1)
European Research Council
(ERC CoG 724373)
Helmholtz Association
(W2/W3-066)
© 2021 Leithner et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (4): e202006081.
Article history
Received:
June 13 2020
Revision Received:
November 25 2020
Accepted:
January 12 2021
Citation
Alexander Leithner, Lukas M. Altenburger, Robert Hauschild, Frank P. Assen, Klemens Rottner, Theresia E.B. Stradal, Alba Diz-Muñoz, Jens V. Stein, Michael Sixt; Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. J Cell Biol 5 April 2021; 220 (4): e202006081. doi: https://doi.org/10.1083/jcb.202006081
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