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多个中心体增强成熟树突状细胞的迁移和免疫细胞效应功能。

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

机构信息

Life and Medical Sciences Institute, Immune and Tumor Biology, University of Bonn, Bonn, Germany.

BIOCEV, First Faculty of Medicine, Charles University, Vestec, Czech Republic.

出版信息

J Cell Biol. 2022 Dec 5;221(12). doi: 10.1083/jcb.202107134. Epub 2022 Oct 10.

DOI:10.1083/jcb.202107134
PMID:36214847
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9555069/
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.

摘要

中心体在免疫细胞相互作用和免疫反应的启动中起着至关重要的作用。在增殖细胞中，中心体数量受到严格控制，通常在 G1 期限制为 1 个，在有丝分裂前限制为 2 个。调节中心体数量的缺陷与细胞转化和肿瘤发生有关。在这里，我们报告了免疫激活过程中白细胞中额外中心体的出现。抗原识别后，树突状细胞经历不完全有丝分裂，并在随后的 G1 期停滞，导致四倍体细胞积累中心体。此外，细胞刺激增加了 polo 样激酶 2 的表达，导致在 G1 期阻滞的细胞中具有两个中心体的二倍体细胞。在细胞迁移过程中，中心体紧密聚集并充当功能性微管组织中心，允许沿着趋化因子梯度增加持久的运动。此外，具有额外中心体的树突状细胞表现出增强的炎症细胞因子分泌和优化的 T 细胞反应。总之，这些结果表明额外中心体在维持细胞和组织稳态方面发挥了以前未被认识到的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8797/9555069/e7b5b242916f/JCB_202107134_Fig10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8797/9555069/be9b9b9344ca/JCB_202107134_FigS1.jpg
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