Centrosome Function and Regulation in Immune Cells - IPBS-Toulouse, Seminar Room

Centrosomes constitute structural elements organizing the mitotic spindle in animal cells for proper chromosome segregation. Centrosome numbers are tightly controlled and limited to one during interphase and two before a cell enters mitosis. Defects in regulating centrosome numbers lead to the presence of amplified centrosomes, which are a hallmark of malignant cells and sufficient to induce tumorigenesis. By contrast, amplified centrosomes are rarely observed in normal somatic cells and often removed during terminal differentiation. We recently demonstrated that primary dendritic cells, which represent the most potent antigen presenting cells of the innate immune system, amplify centrosome numbers upon immune activation. Mature dendritic cells accumulate centrosomes by mitotic defects and show high expression levels of polo-like kinase 2 (PLK2) leading to over-duplication of centrioles in G1-arrested cells. During cell migration, extra centrosomes tightly cluster and act as functional microtubule-organizing centers, which promote persistent locomotion along gradients of chemotactic cues. Moreover, dendritic cells with amplified centrosomes show enhanced secretion of inflammatory cytokines and optimized T cell responses. Our data indicate that amplified centrosomes are not only a marker for malignancy but actually contribute to promote immune cell effector functions. We are further interested in the molecular basis of how extra centrosomes enhance immune responses and contribute to regular cell and tissue homeostasis. To this end, we combine cell-based in vitro assays with studies in living tissues to explore the nature, causes and consequences of centrosome amplification in immune cells.