DNA 损伤信号指导粒细胞中的多体巨细胞命运
Laura Herrtwich1, Indrajit Nanda2, Konstantinos Evangelou3
1Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Center of Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Cell
|January 14, 2017
概括
持续的Toll-like受体2信号驱使巨细胞通过DNA损伤反应而不是融合成为多倍体. 在慢性炎症期间,这种过程塑造了颗粒瘤组织的重塑.
科学领域:
- 免疫学
- 细胞生物学
- 基因组学
背景情况:
- 颗粒瘤是对慢性炎症作出反应的免疫聚合物.
- 颗粒体内的巨细胞子集表现出多样化的基因组内容.
- 长期炎症中巨分化的分子驱动因素尚不清楚.
研究的目的:
- 定义控制巨分化的分子途径,以应对慢性炎症刺激.
- 调查托尔类受体2 (TLR2) 信号在巨命运中的作用.
- 阐明颗粒瘤中多体巨细胞形成的机制.
主要方法:
- 通过持续的TLR2信号诱导的巨分化途径的分析.
- 研究复制应激和DNA损伤反应的激活.
- 对细胞分裂机制和巨细胞的基因组不稳定性的评估.
- 通过TLR2信号对Myc和ATR的调节进行评估.
主要成果:
- 持续的TLR2信号会通过复制应激和DNA损伤反应诱导巨多体化.
- 多倍粒细胞巨是由细胞分裂而不是细胞融合引起的.
- 通过调节Myc和ATR来抑制基因组的不稳定性.
- 一个新的巨分化途径被划定.
结论:
- 持续的TLR2信号促进了巨多重化,这是粒瘤形成的关键事件.
- 这一途径涉及复制应激和DNA损伤反应,产生长寿命的多倍体巨细胞.
- 这些发现将通常与致癌相关的途径与生理免疫反应和组织重塑联系起来.
相关概念视频
Differentiation of Common Myeloid Progenitor Cells
4.1K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
4.1K
Cells of the Innate Immune Response
10.1K
The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
10.1K
Phagocytosis of Apoptotic Cells
5.4K
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...
Normal cells contain receptors that prevent them from being recognized...
5.4K
Immune Surveillance by NK Cells and Phagocytes
9.2K
Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
9.2K
DNA Damage Can Stall the Cell Cycle
3.3K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.3K
DNA Damage can Stall the Cell Cycle
10.3K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.3K


