Cxcr4可从小胶质细胞中区分HSC来源的单核细胞
2020-02-13   阅读:265   来源:自然

德国耶拿大学Ralf Stumm、美国斯隆-凯特琳研究所Frederic Geissmann、Elvira Mass等研究人员合作发现,Cxcr4可从小胶质细胞中区分HSC来源的单核细胞,并揭示其对实验性中风的免疫反应。相关论文于2020年2月10日在线发表于国际学术期刊《自然—神经科学》。

研究人员发现Cxcr4-CreER能够对造血干细胞(HSC)进行永久性基因标记,并从小胶质细胞和其他组织驻留的巨噬细胞中区分HSC来源的单核细胞。在光血栓引起的中风模型中,通过结合Cxcr4-CreER介导的谱系追踪与Cxcr4抑制或条件性Cxcr4敲除,研究人员发现Cxcr4促进初始的单核细胞浸润以及随后单核细胞来源巨噬细胞向梗塞组织的区域限制。短暂局部缺血后,Cxcr4缺乏会减少单核细胞浸润并降低单核细胞来源巨噬细胞中模式识别和防御反应基因的表达。这与小胶质细胞响应的改变和结果的恶化有关。因此,Cxcr4对于脑缺血后先天免疫系统介导的防御反应至关重要。研究人员进一步提出Cxcr4-CreER可作为研究HSC来源细胞功能的通用工具。
 
据了解,单核细胞来源的和组织驻留的巨噬细胞是先天免疫系统在个体发生上独立的组成部分。炎症过程中巨噬细胞表型的变化使它们各自在病理学中的功能评估变得复杂。
 
附:英文原文

Title: Cxcr4 distinguishes HSC-derived monocytes from microglia and reveals monocyte immune responses to experimental stroke

Author: Yves Werner, Elvira Mass, Praveen Ashok Kumar, Thomas Ulas, Kristian Hndler, Arik Horne, Kathrin Klee, Amelie Lupp, Dagmar Schtz, Friederike Saaber, Christoph Redecker, Joachim L. Schultze, Frederic Geissmann, Ralf Stumm

Issue&Volume: 2020-02-10

Abstract: Monocyte-derived and tissue-resident macrophages are ontogenetically distinct components of the innate immune system. Assessment of their respective functions in pathology is complicated by changes to the macrophage phenotype during inflammation. Here we find that Cxcr4-CreER enables permanent genetic labeling of hematopoietic stem cells (HSCs) and distinguishes HSC-derived monocytes from microglia and other tissue-resident macrophages. By combining Cxcr4-CreER-mediated lineage tracing with Cxcr4 inhibition or conditional Cxcr4 ablation in photothrombotic stroke, we find that Cxcr4 promotes initial monocyte infiltration and subsequent territorial restriction of monocyte-derived macrophages to infarct tissue. After transient focal ischemia, Cxcr4 deficiency reduces monocyte infiltration and blunts the expression of pattern recognition and defense response genes in monocyte-derived macrophages. This is associated with an altered microglial response and deteriorated outcomes. Thus, Cxcr4 is essential for an innate-immune-system-mediated defense response after cerebral ischemia. We further propose Cxcr4-CreER as a universal tool to study functions of HSC-derived cells.

DOI: 10.1038/s41593-020-0585-y

编辑:小柯机器人

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