{"id":13435,"date":"2016-12-20T13:54:55","date_gmt":"2016-12-20T12:54:55","guid":{"rendered":"http:\/\/cyber.pixilie.fr\/?post_type=publications&#038;p=13435"},"modified":"2025-09-11T16:48:05","modified_gmt":"2025-09-11T14:48:05","slug":"the-heterogeneity-of-ly6chi-monocytes-controls-their-differentiation-into-inos-macrophages-or-monocyte-derived-dendritic-cells","status":"publish","type":"publication","link":"https:\/\/cri1149.fr\/en\/publication\/the-heterogeneity-of-ly6chi-monocytes-controls-their-differentiation-into-inos-macrophages-or-monocyte-derived-dendritic-cells\/","title":{"rendered":"The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false,"_EventAllDay":false,"_EventTimezone":"","_EventStartDate":"","_EventEndDate":"","_EventStartDateUTC":"","_EventEndDateUTC":"","_EventShowMap":false,"_EventShowMapLink":false,"_EventURL":"","_EventCost":"","_EventCostDescription":"","_EventCurrencySymbol":"","_EventCurrencyCode":"","_EventCurrencyPosition":"","_EventDateTimeSeparator":"","_EventTimeRangeSeparator":"","_EventOrganizerID":[],"_EventVenueID":[],"_OrganizerEmail":"","_OrganizerPhone":"","_OrganizerWebsite":"","_VenueAddress":"","_VenueCity":"","_VenueCountry":"","_VenueProvince":"","_VenueState":"","_VenueZip":"","_VenuePhone":"","_VenueURL":"","_VenueStateProvince":"","_VenueLat":"","_VenueLng":"","_VenueShowMap":false,"_VenueShowMapLink":false},"category_publication":[],"class_list":["post-13435","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"Immunity.","date_de_publication":"20161220","numero_doi":"","equipe":[155],"auteurs-liste":[{"texte_libre":true,"auteur-lien":null,"auteur-text":"Menezes S"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Melandri D"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Anselmi G"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Perchet T"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Loschko J"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Dubrot J"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Patel R"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Gautier EL"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Hugues S"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Longhi MP"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Henry JY"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Quezada SA"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Lauvau G"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Lennon-Dum\u00e9nil AM"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Guti\u00e9rrez-Mart\u00ednez E"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Bessis A"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Gomez-Perdiguero E"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Jacome-Galarza CE"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Garner H"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Geissmann F"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Golub R"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Nussenzweig MC"},{"texte_libre":false,"auteur-lien":13178,"auteur-text":""}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28002729"}],"paragraphe":"<p>[:en]<\/p>\r\n<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">Inflammation triggers the differentiation of Ly6C<sup>hi<\/sup>\u00a0monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3<sup>+<\/sup>CD11c<sup>-<\/sup>MHCII<sup>+<\/sup>PU.1<sup>hi<\/sup>\u00a0subset. This subset acted as a precursor for Fc\u03b3RIII<sup>+<\/sup>PD-L2<sup>+<\/sup>CD209a<sup>+<\/sup>, GM-CSF-dependent moDCs but was distal from the DC lineage, as shown by fate-mapping experiments using Zbtb46. By contrast, Flt3<sup>-<\/sup>CD11c<sup>-<\/sup>MHCII<sup>-<\/sup>PU.1<sup>lo<\/sup>\u00a0monocytes differentiated into Fc\u03b3RIII<sup>+<\/sup>PD-L2<sup>-<\/sup>CD209a<sup>-<\/sup>iNOS<sup>+<\/sup>\u00a0macrophages upon microbial stimulation. Importantly, Sfpi1 haploinsufficiency genetically distinguished the precursor activities of monocytes toward moDCs or microbicidal macrophages. Indeed, Sfpi1<sup>+\/-<\/sup>\u00a0mice had reduced Flt3<sup>+<\/sup>CD11c<sup>-<\/sup>MHCII<sup>+<\/sup>\u00a0monocytes and GM-CSF-dependent Fc\u03b3RIII<sup>+<\/sup>PD-L2<sup>+<\/sup>CD209a<sup>+<\/sup>\u00a0moDCs but generated iNOS<sup>+<\/sup>\u00a0macrophages more efficiently. Therefore, intercellular disparities of PU.1 expression within naive monocytes segregate progenitor activity for inflammatory iNOS<sup>+<\/sup>\u00a0macrophages or moDCs.<\/p>\r\n<\/div>\r\n<p>[:]<\/p>","paragraphe_en":"<p>[:en]<\/p>\r\n<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">Inflammation triggers the differentiation of Ly6C<sup>hi<\/sup>\u00a0monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3<sup>+<\/sup>CD11c<sup>-<\/sup>MHCII<sup>+<\/sup>PU.1<sup>hi<\/sup>\u00a0subset. This subset acted as a precursor for Fc\u03b3RIII<sup>+<\/sup>PD-L2<sup>+<\/sup>CD209a<sup>+<\/sup>, GM-CSF-dependent moDCs but was distal from the DC lineage, as shown by fate-mapping experiments using Zbtb46. By contrast, Flt3<sup>-<\/sup>CD11c<sup>-<\/sup>MHCII<sup>-<\/sup>PU.1<sup>lo<\/sup>\u00a0monocytes differentiated into Fc\u03b3RIII<sup>+<\/sup>PD-L2<sup>-<\/sup>CD209a<sup>-<\/sup>iNOS<sup>+<\/sup>\u00a0macrophages upon microbial stimulation. Importantly, Sfpi1 haploinsufficiency genetically distinguished the precursor activities of monocytes toward moDCs or microbicidal macrophages. Indeed, Sfpi1<sup>+\/-<\/sup>\u00a0mice had reduced Flt3<sup>+<\/sup>CD11c<sup>-<\/sup>MHCII<sup>+<\/sup>\u00a0monocytes and GM-CSF-dependent Fc\u03b3RIII<sup>+<\/sup>PD-L2<sup>+<\/sup>CD209a<sup>+<\/sup>\u00a0moDCs but generated iNOS<sup>+<\/sup>\u00a0macrophages more efficiently. Therefore, intercellular disparities of PU.1 expression within naive monocytes segregate progenitor activity for inflammatory iNOS<sup>+<\/sup>\u00a0macrophages or moDCs.<\/p>\r\n<\/div>\r\n<p>[:]<\/p>","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells - CRI<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/cri1149.fr\/publication\/the-heterogeneity-of-ly6chi-monocytes-controls-their-differentiation-into-inos-macrophages-or-monocyte-derived-dendritic-cells\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells - 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