title: Autophagy is required for CSF-1-induced macrophagic differentiation and acquisition of phagocytic functions.
abstract: Autophagy is the process by which superfluous or damaged macromolecules or organelles are degraded by the lysosome. Pharmacologic and genetic evidence indicates that autophagy plays pleiotropic functions in cellular homeostasis, development, survival, and differentiation. The differentiation of human blood monocytes into macrophages is a caspase-dependent process when triggered ex vivo by colony stimulating factor-1. We show here, using pharmacologic inhibitors, siRNA approaches, and Atg7-/- mice, that autophagy initiated by ULK1 is required for proper colony stimulating factor-1-driven differentiation of human and murine monocytes. We also unravel a role for autophagy in macrophage acquisition of phagocytic functions. Collectively, these findings highlight an unexpected and essential role of autophagy during monocyte differentiation and acquisition of macrophage functions.
authors.affiliation: Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Nice, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jacquel
authors.forename: Sandrine
authors.initials: S
authors.lastname: Obba
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
authors.forename: Maeva
authors.initials: M
authors.lastname: Dufies
authors.forename: Guillaume
authors.initials: G
authors.lastname: Robert
authors.forename: Pierre
authors.initials: P
authors.lastname: Gounon
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lemichez
authors.forename: Frederic
authors.initials: F
authors.lastname: Luciano
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Patrick
authors.initials: P
authors.lastname: Auberger
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D000071189:Autophagy-Related Protein-1 Homolog; D002401:Cathepsin B / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D016173:Macrophage Colony-Stimulating Factor; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C112444:Ulk1 protein, mouse; D002401:Cathepsin B; D000071193:Autophagy-Related Protein 7