PMID- 33533935 OWN - NLM STAT- MEDLINE DCOM- 20210921 LR - 20211006 IS - 1540-8140 (Electronic) IS - 0021-9525 (Print) IS - 0021-9525 (Linking) VI - 220 IP - 4 DP - 2021 Apr 5 TI - Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. LID - 10.1083/jcb.202006081 [doi] LID - e202006081 AB - 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. CI - (c) 2021 Leithner et al. FAU - Leithner, Alexander AU - Leithner A AD - Institute of Science and Technology Austria, Klosterneuburg, Austria. AD - Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK. FAU - Altenburger, Lukas M AU - Altenburger LM AD - Department of Oncology, Microbiology and Immunology, University of Fribourg, Fribourg, Switzerland. FAU - Hauschild, Robert AU - Hauschild R AD - Institute of Science and Technology Austria, Klosterneuburg, Austria. FAU - Assen, Frank P AU - Assen FP AD - Institute of Science and Technology Austria, Klosterneuburg, Austria. FAU - Rottner, Klemens AU - Rottner K AD - Zoological Institute, Technical University Braunschweig, Braunschweig, Germany. AD - Department of Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany. FAU - Stradal, Theresia E B AU - Stradal TEB AD - Department of Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany. FAU - Diz-Munoz, Alba AU - Diz-Munoz A AD - Cell Biology and Biophysics Units, European Molecular Biology Laboratory, Heidelberg, Germany. FAU - Stein, Jens V AU - Stein JV AD - Department of Oncology, Microbiology and Immunology, University of Fribourg, Fribourg, Switzerland. FAU - Sixt, Michael AU - Sixt M AD - Institute of Science and Technology Austria, Klosterneuburg, Austria. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Actins) RN - 0 (Icam1 protein, mouse) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Actins/genetics/*immunology MH - Animals MH - Cell Adhesion/genetics/immunology MH - Cell Communication/genetics/*immunology MH - Cell Proliferation/genetics MH - Dendritic Cells/*immunology MH - Female MH - Immunological Synapses/genetics/*immunology MH - Intercellular Adhesion Molecule-1/genetics/immunology MH - Male MH - Mice MH - Mice, Knockout MH - T-Lymphocytes/*immunology PMC - PMC7863705 EDAT- 2021/02/04 06:00 MHDA- 2021/09/22 06:00 PMCR- 2021/10/05 CRDT- 2021/02/03 12:13 PHST- 2020/06/13 00:00 [received] PHST- 2020/11/25 00:00 [revised] PHST- 2021/01/12 00:00 [accepted] PHST- 2021/02/03 12:13 [entrez] PHST- 2021/02/04 06:00 [pubmed] PHST- 2021/09/22 06:00 [medline] PHST- 2021/10/05 00:00 [pmc-release] AID - 211749 [pii] AID - jcb.202006081 [pii] AID - 10.1083/jcb.202006081 [doi] PST - ppublish SO - J Cell Biol. 2021 Apr 5;220(4):e202006081. doi: 10.1083/jcb.202006081.