CXCR4和CCR2之间的相互作用调节了树突细胞祖先的骨髓退出
Mariana Pereira da Costa1, Carlos M Minutti1, Cécile Piot1
1Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Cell reports
|July 31, 2023
概括
研究人员确定了两种骨髓原生种群CXCR4lo和CXCR4hi,对于补充免疫细胞至关重要. 在炎症和感染期间,CXCR4lo细胞是免疫细胞调动的关键.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 血液形成 血液形成 血液形成
背景情况:
- 传统的树突细胞 (cDC) 对于启动免疫反应至关重要,并且存在于大多数组织中.
- 不断补充cDCs是必不可少的,源自骨髓前代 (pre-cDCs) 循环以填充组织.
- 炎症可以加速cDC的产生,这个过程被称为紧急cDCpoiesis.
研究的目的:
- 为了确定参与cDC补充的不同的骨髓原始种群.
- 阐明调节骨髓前cDCs调动的机制.
- 了解化基因信号如何影响稳定状态和紧急cDC产生.
主要方法:
- 流细胞计以区分基于CXCR4表达的前cDC群体.
- 在体内研究以追踪细胞迁移和调动.
- 对化学受体表达 (CXCR4,CCR2) 和信号通路 (I型IFN) 的分析.
主要成果:
- 确定了两种骨髓前cDC种群,根据CXCR4表达水平 (CXCR4lo和CXCR4hi) 进行区分.
- CXCR4lo前cDCs代表了迁徙池,能够离开骨髓,并在免疫挑战期间迅速动员.
- 在稳定状态下,骨髓的前cDC输出部分依赖于CCR2,I型IFN信号增强了CCR2的表达,并在流感A病毒感染期间增加了输出.
结论:
- CXCR4表达式定义了功能上不同的骨髓前cDC子集.
- 化基因受体动力学,特别是CXCR4和CCR2,是恒温和应急树突细胞生产的关键调节者.
- 保持和流出信号之间的平衡控制了免疫原始体的贩运.
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