title: Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis.
abstract: Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense. Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential. However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined. Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression. We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes. Furthermore, we have established that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly6C(-) cells and that the abundance of Ly6C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Simon
authors.initials: S
authors.lastname: Yona
authors.forename: Ki-Wook
authors.initials: KW
authors.lastname: Kim
authors.forename: Yochai
authors.initials: Y
authors.lastname: Wolf
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.forename: Diana
authors.initials: D
authors.lastname: Varol
authors.forename: Michal
authors.initials: M
authors.lastname: Breker
authors.forename: Dalit
authors.initials: D
authors.lastname: Strauss-Ayali
authors.forename: Sergey
authors.initials: S
authors.lastname: Viukov
authors.forename: Martin
authors.initials: M
authors.lastname: Guilliams
authors.forename: Alexander
authors.initials: A
authors.lastname: Misharin
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
authors.forename: Harris
authors.initials: H
authors.lastname: Perlman
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Elazar
authors.initials: E
authors.lastname: Zelzer
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D006706:Homeostasis / Q000276:immunology; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D023461:Myeloid Progenitor Cells / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; C494192:Ly-6C antigen, mouse; D019707:Receptors, Chemokine