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dc.contributor.authorGamrekelashvili, Jaba
dc.contributor.authorKapanadze, Tamar
dc.contributor.authorSablotny, Stefan
dc.contributor.authorRatiu, Corina
dc.contributor.authorDastagir, Khaled
dc.contributor.authorLochner, Matthias
dc.contributor.authorKarbach, Susanne
dc.contributor.authorWenzel, Philip
dc.contributor.authorSitnow, Andre
dc.contributor.authorFleig, Susanne
dc.contributor.authorSparwasser, Tim
dc.contributor.authorKalinke, Ulrich
dc.contributor.authorHolzmann, Bernhard
dc.contributor.authorHaller, Hermann
dc.contributor.authorLimbourg, Florian P
dc.date.accessioned2020-11-16T15:27:02Z
dc.date.available2020-11-16T15:27:02Z
dc.date.issued2020-07-29
dc.identifier.citationElife. 2020 Jul 29;9:e57007. doi: 10.7554/eLife.57007.en_US
dc.identifier.pmid32723480
dc.identifier.doi10.7554/eLife.57007
dc.identifier.urihttp://hdl.handle.net/10033/622587
dc.description.abstractConventional Ly6Chi monocytes have developmental plasticity for a spectrum of differentiated phagocytes. Here we show, using conditional deletion strategies in a mouse model of Toll-like receptor (TLR) 7-induced inflammation, that the spectrum of developmental cell fates of Ly6Chi monocytes, and the resultant inflammation, is coordinately regulated by TLR and Notch signaling. Cell-intrinsic Notch2 and TLR7-Myd88 pathways independently and synergistically promote Ly6Clo patrolling monocyte development from Ly6Chi monocytes under inflammatory conditions, while impairment in either signaling axis impairs Ly6Clo monocyte development. At the same time, TLR7 stimulation in the absence of functional Notch2 signaling promotes resident tissue macrophage gene expression signatures in monocytes in the blood and ectopic differentiation of Ly6Chi monocytes into macrophages and dendritic cells, which infiltrate the spleen and major blood vessels and are accompanied by aberrant systemic inflammation. Thus, Notch2 is a master regulator of Ly6Chi monocyte cell fate and inflammation in response to TLR signaling.en_US
dc.language.isoenen_US
dc.publisherelife Sciencesen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectTLR signalingen_US
dc.subjectimmunologyen_US
dc.subjectinflammationen_US
dc.subjectmacrophage differentiationen_US
dc.subjectmonocytes and macrophagesen_US
dc.subjectmouseen_US
dc.subjectnotch signalingen_US
dc.titleNotch and TLR signaling coordinate monocyte cell fate and inflammation.en_US
dc.typeArticleen_US
dc.identifier.eissn2050-084X
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journaleLifeen_US
dc.source.volume9
refterms.dateFOA2020-11-16T15:27:03Z
dc.source.journaltitleeLife
dc.source.countryInternational
dc.source.countryInternational
dc.source.countryInternational
dc.source.countryEngland


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