title: Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes.
abstract: Despite accumulating evidence suggesting local self-maintenance of tissue macrophages in the steady state, the dogma remains that tissue macrophages derive from monocytes. Using parabiosis and fate-mapping approaches, we confirmed that monocytes do not show significant contribution to tissue macrophages in the steady state. Similarly, we found that after depletion of lung macrophages, the majority of repopulation occurred by stochastic cellular proliferation in situ in a macrophage colony-stimulating factor (M-Csf)- and granulocyte macrophage (GM)-CSF-dependent manner but independently of interleukin-4. We also found that after bone marrow transplantation, host macrophages retained the capacity to expand when the development of donor macrophages was compromised. Expansion of host macrophages was functional and prevented the development of alveolar proteinosis in mice transplanted with GM-Csf-receptor-deficient progenitors. Collectively, these results indicate that tissue-resident macrophages and circulating monocytes should be classified as mononuclear phagocyte lineages that are independently maintained in the steady state.
authors.affiliation: Department of Oncological Sciences and Tisch Cancer Institute, Critical Care and Sleep Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Daigo
authors.initials: D
authors.lastname: Hashimoto
authors.forename: Andrew
authors.initials: A
authors.lastname: Chow
authors.forename: Clara
authors.initials: C
authors.lastname: Noizat
authors.forename: Pearline
authors.initials: P
authors.lastname: Teo
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Beasley
authors.forename: Marylene
authors.initials: M
authors.lastname: Leboeuf
authors.forename: Christian D
authors.initials: CD
authors.lastname: Becker
authors.forename: Peter
authors.initials: P
authors.lastname: See
authors.forename: Jeremy
authors.initials: J
authors.lastname: Price
authors.forename: Daniel
authors.initials: D
authors.lastname: Lucas
authors.forename: Melanie
authors.initials: M
authors.lastname: Greter
authors.forename: Arthur
authors.initials: A
authors.lastname: Mortha
authors.forename: Scott W
authors.initials: SW
authors.lastname: Boyer
authors.forename: E Camilla
authors.initials: EC
authors.lastname: Forsberg
authors.forename: Masato
authors.initials: M
authors.lastname: Tanaka
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
mesh_terms: D000328:Adult; D000818:Animals; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010227:Parabiosis; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics
chemical_list: D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor