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》。


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


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