Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells
Weier A-K, Homrich M, Ebbinghaus S, Juda P, Miková E, Hauschild R, Zhang L, Quast T, Mass E, Schlitzer A, Kolanus W, Burgdorf S, Gruß OJ, Hons M, Wieser S, Kiermaier E. 2022. Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells. Journal of Cell Biology. 221(12), e202107134.
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Author
Weier, Ann-Kathrin;
Homrich, Mirka;
Ebbinghaus, Stephanie;
Juda, Pavel;
Miková, Eliška;
Hauschild, RobertISTA ;
Zhang, Lili;
Quast, Thomas;
Mass, Elvira;
Schlitzer, Andreas;
Kolanus, Waldemar;
Burgdorf, Sven
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All
Department
Abstract
Centrosomes play a crucial role during immune cell interactions and initiation of the immune response. In proliferating cells, centrosome numbers are tightly controlled and generally limited to one in G1 and two prior to mitosis. Defects in regulating centrosome numbers have been associated with cell transformation and tumorigenesis. Here, we report the emergence of extra centrosomes in leukocytes during immune activation. Upon antigen encounter, dendritic cells pass through incomplete mitosis and arrest in the subsequent G1 phase leading to tetraploid cells with accumulated centrosomes. In addition, cell stimulation increases expression of polo-like kinase 2, resulting in diploid cells with two centrosomes in G1-arrested cells. During cell migration, centrosomes tightly cluster and act as functional microtubule-organizing centers allowing for increased persistent locomotion along gradients of chemotactic cues. Moreover, dendritic cells with extra centrosomes display enhanced secretion of inflammatory cytokines and optimized T cell responses. Together, these results demonstrate a previously unappreciated role of extra centrosomes for regular cell and tissue homeostasis.
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Publishing Year
Date Published
2022-12-05
Journal Title
Journal of Cell Biology
Publisher
Rockefeller University Press
Acknowledgement
We thank Markéta Dalecká and Irena Krejzová for their support with FIB-SEM imaging, the Imaging Methods Core Facility at BIOCEV supported by the Ministry of Education, Youth and Sports Czech Republic (Large RI Project LM2018129 Czech-BioImaging), and European Regional Development Fund (project No. CZ.02.1.01/0.0/0.0/18_046/0016045) for their support with obtaining imaging data presented in this paper. The authors further thank Andreas Villunger, Florian Gärtner, Frank Bradke, and Sarah Förster for helpful discussions; Andy Zielinski for help with statistics; and Björn Weiershausen for assisting with figure illustration.
This work was funded by a fellowship of the Ministry of Innovation, Science and Research of North-Rhine-Westphalia (AZ: 421-8.03.03.02-137069) to E. Kiermaier and the Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany’s Excellence Strategy – EXC 2151 – 390873048. R. Hauschild was funded by grant number 2020-225401 from the Chan Zuckerberg Initiative Donor-Advised Fund, an advised fund of Silicon Valley Community Foundation. M. Hons is supported by Czech Science Foundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013.
Volume
221
Issue
12
Article Number
e202107134
ISSN
eISSN
IST-REx-ID
Cite this
Weier A-K, Homrich M, Ebbinghaus S, et al. Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells. Journal of Cell Biology. 2022;221(12). doi:10.1083/jcb.202107134
Weier, A.-K., Homrich, M., Ebbinghaus, S., Juda, P., Miková, E., Hauschild, R., … Kiermaier, E. (2022). Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.202107134
Weier, Ann-Kathrin, Mirka Homrich, Stephanie Ebbinghaus, Pavel Juda, Eliška Miková, Robert Hauschild, Lili Zhang, et al. “Multiple Centrosomes Enhance Migration and Immune Cell Effector Functions of Mature Dendritic Cells.” Journal of Cell Biology. Rockefeller University Press, 2022. https://doi.org/10.1083/jcb.202107134.
A.-K. Weier et al., “Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells,” Journal of Cell Biology, vol. 221, no. 12. Rockefeller University Press, 2022.
Weier A-K, Homrich M, Ebbinghaus S, Juda P, Miková E, Hauschild R, Zhang L, Quast T, Mass E, Schlitzer A, Kolanus W, Burgdorf S, Gruß OJ, Hons M, Wieser S, Kiermaier E. 2022. Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells. Journal of Cell Biology. 221(12), e202107134.
Weier, Ann-Kathrin, et al. “Multiple Centrosomes Enhance Migration and Immune Cell Effector Functions of Mature Dendritic Cells.” Journal of Cell Biology, vol. 221, no. 12, e202107134, Rockefeller University Press, 2022, doi:10.1083/jcb.202107134.
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