| Literature DB >> 32042176 |
Yves Werner1, Elvira Mass2,3, Praveen Ashok Kumar1, Thomas Ulas4,5, Kristian Händler4,5, Arik Horne4, Kathrin Klee4, Amelie Lupp1, Dagmar Schütz1, Friederike Saaber1, Christoph Redecker6, Joachim L Schultze4,5, Frederic Geissmann7, Ralf Stumm8.
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.Entities:
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Year: 2020 PMID： 32042176 PMCID： PMC7523735 DOI： 10.1038/s41593-020-0585-y
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884