title: Type 1 interferons contribute to the clearance of senescent cell.
abstract: The major known function of cytokines that belong to type I interferons (IFN, including IFNα and IFNβ) is to mount the defense against viruses. This function also protects the genetic information of host cells from alterations in the genome elicited by some of these viruses. Furthermore, recent studies demonstrated that IFN also restrict proliferation of damaged cells by inducing cell senescence. Here we investigated the subsequent role of IFN in elimination of the senescent cells. Our studies demonstrate that endogenous IFN produced by already senescent cells contribute to increased expression of the natural killer (NK) receptor ligands, including MIC-A and ULBP2. Furthermore, neutralization of endogenous IFN or genetic ablation of its receptor chain IFNAR1 compromises the recognition of senescent cells and their clearance in vitro and in vivo. We discuss the role of IFN in protecting the multi-cellular host from accumulation of damaged senescent cells and potential significance of this mechanism in human cancers.
authors.affiliation: a Department of Biomedical Sciences ; School of Veterinary Medicine ; University of Pennsylvania ; Philadelphia , PA USA.
authors.forename: Yuliya V
authors.initials: YV
authors.lastname: Katlinskaya
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Carbone
authors.forename: Qiujing
authors.initials: Q
authors.lastname: Yu
authors.forename: Serge Y
authors.initials: SY
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D058851:GPI-Linked Proteins / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007370:Interferon Type I / Q000494:pharmacology / Q000502:physiology*; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism; D011371:Progeria / Q000473:pathology; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D014898:Werner Syndrome / Q000473:pathology
chemical_list: D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; C508032:Ifnar1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D007370:Interferon Type I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; C423230:ULBP2 protein, human; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta
keywords: DDR, DNA damage response; HGPS, Hutchinson-Gilford progeria syndrome; IFN, type I interferons; IFNAR1, type I IFN receptor; NK cells; NK, natural killer cells; SA-βGal, senescence-associated β-galactosidase; WS, Werner syndrome; interferon; senescence; senescent cell clearance