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dc.contributor.authorBeattie, Lynette
dc.contributor.authorSawtell, Amy
dc.contributor.authorMann, Jason
dc.contributor.authorFrame, Teija CM
dc.contributor.authorTeal, Bianca
dc.contributor.authorRivera, Fabian de Labastida
dc.contributor.authorBrown, Najmeeyah
dc.contributor.authorWalwyn-Brown, Katherine
dc.contributor.authorMoore, John WJ
dc.contributor.authorMacDonald, Sandy
dc.contributor.authorLim, Eng-Kiat
dc.contributor.authorDalton, Jane E
dc.contributor.authorEngwerda, Christian R
dc.contributor.authorMacDonald, Kelli P
dc.contributor.authorKaye, Paul M
dc.date.accessioned2021-07-16T05:55:59Z
dc.date.available2021-07-16T05:55:59Z
dc.date.issued2016
dc.identifier.issn0168-8278en_US
dc.identifier.doi10.1016/j.jhep.2016.05.037en_US
dc.identifier.urihttp://hdl.handle.net/10072/406091
dc.description.abstractBackground & Aims: Kupffer cells (KCs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. Recent studies have identified KCs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. Although it is now established that following local tissue injury, bone marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, the extent to which newly differentiated macrophages functionally resemble the KCs they have replaced has not been extensively studied. Methods: We studied the two populations of KCs using intravital microscopy, morphometric analysis and gene expression profiling. An ion homeostasis gene signature, including genes associated with scavenger receptor function and extracellular matrix deposition, allowed discrimination between these two KC sub-types. Results: Bone marrow derived “KCs” accumulating as a result of genotoxic injury, resemble but are not identical to their yolk sac counterparts. Reflecting the differential expression of scavenger receptors, yolk sac-derived KCs were more effective at accumulating acetylated low density lipoprotein, whereas surprisingly, they were poorer than bone marrow-derived KCs when assessed for uptake of a range of bacterial pathogens. The two KC populations were almost indistinguishable in regard to i) response to lipopolysaccharide challenge, ii) phagocytosis of effete red blood cells and iii) their ability to contain infection and direct granuloma formation against Leishmania donovani, a KC-tropic intracellular parasite. Conclusions: Bone marrow-derived KCs differentiate locally to resemble yolk sac-derived KC in most but not all respects, with implications for models of infectious diseases, liver injury and bone marrow transplantation. In addition, the gene signature we describe adds to the tools available for distinguishing KC subpopulations based on their ontology. Lay summary: Liver macrophages play a major role in the control of infections in the liver and in the pathology associated with chronic liver diseases. It was recently shown that liver macrophages can have two different origins, however, the extent to which these populations are functionally distinct remains to be fully addressed. Our study demonstrates that whilst liver macrophages share many features in common, regardless of their origin, some subtle differences in function exist. Data repository: Gene expression data are available from the European Bioinformatics Institute ArrayExpress data repository (accession number E-MTAB-4954).en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherElsevieren_US
dc.relation.ispartofpagefrom758en_US
dc.relation.ispartofpageto768en_US
dc.relation.ispartofissue4en_US
dc.relation.ispartofjournalJournal of Hepatologyen_US
dc.relation.ispartofvolume65en_US
dc.subject.fieldofresearchClinical Sciencesen_US
dc.subject.fieldofresearchPublic Health and Health Servicesen_US
dc.subject.fieldofresearchcode1103en_US
dc.subject.fieldofresearchcode1117en_US
dc.subject.keywordsScience & Technologyen_US
dc.subject.keywordsLife Sciences & Biomedicineen_US
dc.subject.keywordsGastroenterology & Hepatologyen_US
dc.subject.keywordsKupffer cellsen_US
dc.subject.keywordsLiver macrophagesen_US
dc.titleBone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functionsen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Articlesen_US
dcterms.bibliographicCitationBeattie, L; Sawtell, A; Mann, J; Frame, TCM; Teal, B; Rivera, FDL; Brown, N; Walwyn-Brown, K; Moore, JWJ; MacDonald, S; Lim, E-K; Dalton, JE; Engwerda, CR; MacDonald, KP; Kaye, PM, Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions, Journal of Hepatology, 2016, 65 (4), pp. 758-768en_US
dcterms.dateAccepted2016-05-25
dc.date.updated2021-07-16T01:50:47Z
gro.hasfulltextNo Full Text
gro.griffith.authorEngwerda, Christian R.


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