4.7 Article

Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells

Journal

JOURNAL OF CELL BIOLOGY
Volume 221, Issue 12, Pages -

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202107134

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Funding

  1. Ministry of Education, Youth and Sports Czech Republic [LM2018129]
  2. European Regional Development Fund [CZ.02.1.01/0.0/0.0/18_046/0016045]
  3. Ministry of Innovation, Science and Research of North-Rhine-Westphalia [AZ: 421-8.03.03.02-137069]
  4. Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany's Excellence Strategy [EXC 2151 - 390873048]
  5. Chan Zuckerberg Initiative Donor-Advised Fund [2020-225401]
  6. Silicon Valley Community Foundation
  7. Czech Science Foundation [GACR 20-24603Y]
  8. Charles University [PRIMUS/20/MED/013]

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Centrosomes play a crucial role in immune cell interactions and immune response initiation. Immune activation leads to the emergence of extra centrosomes in leukocytes, which contribute to cell migration, secretion of inflammatory cytokines, and optimized T cell responses. These findings highlight the previously underestimated importance of extra centrosomes in cell and tissue homeostasis.
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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