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

被引:13
|
作者
Weier, Ann-Kathrin [1 ]
Homrich, Mirka [1 ]
Ebbinghaus, Stephanie [1 ]
Juda, Pavel [2 ]
Mikova, Eliska [2 ]
Hauschild, Robert [3 ]
Zhang, Lili [4 ]
Quast, Thomas [5 ]
Mass, Elvira [6 ]
Schlitzer, Andreas [4 ]
Kolanus, Waldemar [5 ]
Burgdorf, Sven [7 ]
Gruss, Oliver J. [8 ]
Hons, Miroslav [2 ]
Wieser, Stefan [9 ]
Kiermaier, Eva [1 ]
机构
[1] Univ Bonn, Life & Med Sci Inst, Immune & Tumor Biol, Bonn, Germany
[2] Charles Univ Prague, Fac Med 1, BIOCEV, Vestec, Czech Republic
[3] IST Austria, Klosterneuburg, Austria
[4] Univ Bonn, Life & Med Sci Inst, Quantitat Syst Biol, Bonn, Germany
[5] Univ Bonn, Life & Med Sci Inst, Mol Immunol & Cell Biol, Bonn, Germany
[6] Univ Bonn, Life & Med Sci Inst, Dev Biol Immune Syst, Bonn, Germany
[7] Univ Bonn, Life & Med Sci Inst, Cellular Immunol, Bonn, Germany
[8] Univ Bonn, Inst Genet, Bonn, Germany
[9] Barcelona Inst Sci & Technol, Inst Ciencies Foton, Castelldefels, Spain
来源
JOURNAL OF CELL BIOLOGY | 2022年 / 221卷 / 12期
关键词
CENTRIOLE DUPLICATION; IN-VIVO; EXTRA CENTROSOMES; CANCER-CELLS; MICROTUBULE; CYCLE; PROTEIN; AMPLIFICATION; POLARIZATION; MATURATION;
D O I
10.1083/jcb.202107134
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
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页数:38
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