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Cancer Biol Ther. 2015;16(8):1214-9. doi: 10.1080/15384047.2015.1056419. Epub 2015 Jun 5.

Type 1 interferons contribute to the clearance of senescent cell.

Author information

1
a Department of Biomedical Sciences ; School of Veterinary Medicine ; University of Pennsylvania ; Philadelphia , PA USA.

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.

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

PMID:
26046815
PMCID:
PMC4622626
DOI:
10.1080/15384047.2015.1056419
[Indexed for MEDLINE]
Free PMC Article

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