title: Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes.
abstract: It is thought that monocytes rapidly differentiate to macrophages or dendritic cells (DCs) upon leaving blood. Here we have shown that Ly-6C⁺ monocytes constitutively trafficked into skin, lung, and lymph nodes (LNs). Entry was unaffected in gnotobiotic mice. Monocytes in resting lung and LN had similar gene expression profiles to blood monocytes but elevated transcripts of a limited number of genes including cyclo-oxygenase-2 (COX-2) and major histocompatibility complex class II (MHCII), induced by monocyte interaction with endothelium. Parabiosis, bromodoxyuridine (BrdU) pulse-chase analysis, and intranasal instillation of tracers indicated that instead of contributing to resident macrophages in the lung, recruited endogenous monocytes acquired antigen for carriage to draining LNs, a function redundant with DCs though differentiation to DCs did not occur. Thus, monocytes can enter steady-state nonlymphoid organs and recirculate to LNs without differentiation to macrophages or DCs, revising a long-held view that monocytes become tissue-resident macrophages by default.
authors.affiliation: Department of Pediatrics at National Jewish Health, Denver, CO 80206, USA; Integrated Department of Immunology, University of Colorado, Denver, CO 80206, USA; Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Jakubzick
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Gautier
authors.forename: Sophie L
authors.initials: SL
authors.lastname: Gibbings
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Sojka
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlitzer
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Johnson
authors.forename: Stoyan
authors.initials: S
authors.lastname: Ivanov
authors.forename: Qiaonan
authors.initials: Q
authors.lastname: Duan
authors.forename: Shashi
authors.initials: S
authors.lastname: Bala
authors.forename: Tracy
authors.initials: T
authors.lastname: Condon
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: John R
authors.initials: JR
authors.lastname: Grainger
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.forename: Avi
authors.initials: A
authors.lastname: Ma'ayan
authors.forename: David W H
authors.initials: DW
authors.lastname: Riches
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Yokoyama
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Peter M
authors.initials: PM
authors.lastname: Henson
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000166:cytology; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D012867:Skin / Q000166:cytology
chemical_list: D000950:Antigens, Ly; D000949:Histocompatibility Antigens Class II; C494192:Ly-6C antigen, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2