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

   

Authors:	Werner, Y.; Mass, E.; Ashok Kumar, P.; Ulas, T.; Händler, K.; Horne, A.; Klee, K.; Lupp, A.; Schütz, D.; Saaber, F.; Redecker, C.; Schultze, J. L.; Geissmann, F.; Stumm, R.
Article Title:	Cxcr4 distinguishes HSC-derived monocytes from microglia and reveals monocyte immune responses to experimental stroke
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. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Keywords:	adult; controlled study; nonhuman; animal cell; mouse; animal tissue; animal experiment; animal model; cellular immunity; innate immunity; cxcr4 gene; hematopoietic stem cell; monocyte; brain ischemia; chemokine receptor cxcr4; microglia; male; female; priority journal; article; experimental stroke
Journal Title:	Nature Neuroscience
Volume:	23
Issue:	3
ISSN:	1097-6256
Publisher:	Nature Publishing Group
Date Published:	2020-03-01
Start Page:	351
End Page:	362
Language:	English
DOI:	10.1038/s41593-020-0585-y
PUBMED:	32042176
PROVIDER:	scopus
PMCID:	PMC7523735
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079450281&doi=10.1038%2fs41593-020-0585-y&partnerID=40&md5=d1f040d2273a692bcc9f1ac205cbb239
Notes:	Article -- Export Date: 1 April 2020 -- Source: Scopus

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