title: Involvement of autophagy in NK cell development and function.
abstract: Natural killer (NK) cells are the prototypical members of the recently identified family of innate lymphoid cells (ILCs). Thanks to their cytotoxic and secretory functions, NK cells play a key role in the immune response to cells experiencing various forms of stress, including viral infection and malignant transformation. Autophagy is a highly conserved network of degradative pathways that participate in the maintenance of cellular and organismal homeostasis as they promote adaptation to adverse microenvironmental conditions. The relevance of autophagy in the development and functionality of cellular components of the adaptive immune system is well established. Conversely, whether autophagy also plays an important role in the biology of ILC populations such as NK cells has long remained elusive. Recent experimental evidence shows that ablating Atg5 (autophagy-related 5, an essential component of the autophagic machinery) in NK cells and other specific ILC populations results in progressive mitochondrial damage, reactive oxygen species (ROS) overgeneration, and regulated cell death, hence interrupting ILC development. Moreover, disrupting the interaction of ATG7 with phosphorylated FOXO1 (forkhead box O1) in the cytosol of immature NK cells prevents autophagic responses that are essential for NK cell maturation. These findings suggest that activating autophagy may support the maturation of NK cells and other ILCs that manifest antiviral and anticancer activity.
authors.affiliation: a Departamento de Biología Funcional, Área de Inmunología , Universidad de Oviedo, IUOPA , Oviedo , Asturias , Spain.|b Hospital Universitario Central de Asturias , Oviedo , Asturias , Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: López-Soto
authors.affiliation: c Equipe 11 labellisée par la Ligue contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d INSERM, U1138 , Paris , France.|e Université Paris Descartes/Paris V, Sorbonne Paris Cité , Paris , France.|f Université Pierre et Marie Curie/Paris VI , Paris , France.|g Metabolomics and Cell Biology Platforms , Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Bravo-San Pedro
authors.affiliation: c Equipe 11 labellisée par la Ligue contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d INSERM, U1138 , Paris , France.|e Université Paris Descartes/Paris V, Sorbonne Paris Cité , Paris , France.|f Université Pierre et Marie Curie/Paris VI , Paris , France.|g Metabolomics and Cell Biology Platforms , Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.|h Pôle de Biologie , Hopitâl Européen George Pompidou, AP-HP , Paris , France.|i Department of Women's and Children's Health , Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: c Equipe 11 labellisée par la Ligue contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d INSERM, U1138 , Paris , France.|e Université Paris Descartes/Paris V, Sorbonne Paris Cité , Paris , France.|f Université Pierre et Marie Curie/Paris VI , Paris , France.|j Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.|k Department of Radiation Oncology , Weill Cornell Medical College , New York , NY , USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.affiliation: a Departamento de Biología Funcional, Área de Inmunología , Universidad de Oviedo, IUOPA , Oviedo , Asturias , Spain.
authors.forename: Segundo
authors.initials: S
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D001343:Autophagy; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological
keywords: FOXO1AAA; IL-15; MTOR; anticancer immunosurveillance; mitophagy; rapamycin