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

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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.
Funding Information
  • Ministry of Innovation, Science and Research of North-Rhine-Westphalia (421-8.03.03.02-137069)
  • Deutsche Forschungsgemeinschaft (EXC 2151 – 390873048)
  • Chan Zuckerberg Initiative (2020-225401)
  • Silicon Valley Community Foundation
  • Czech Science Foundation (GACR 20-24603Y)
  • Charles University (PRIMUS/20/MED/013)

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