Granule exocytosis mediates immune surveillance of senescent cells

Sagiv, A., Biran, A., Yon, M., Simon, J., Lowe, S. W., Krizhanovsky, V. (April 2013) Granule exocytosis mediates immune surveillance of senescent cells. Oncogene, 32 (15). pp. 1971-7. ISSN 1476-5594 (Electronic)0950-9232 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22751116/
DOI: 10.1038/onc.2012.206

Abstract

Senescence is a stable cell cycle arrest program that contributes to tumor suppression, organismal aging and certain wound healing responses. During liver fibrosis, for example, hepatic stellate cells initially proliferate and secrete extracellular matrix components that produce fibrosis; however, these cells eventually senesce and are cleared by immune cells, including natural killer (NK) cells. Here, we examine how NK cells target senescent cells and assess the impact of this process on liver fibrosis. We show that granule exocytosis, but not death-receptor-mediated apoptosis, is required for NK-cell-mediated killing of senescent cells. This pathway bias is due to upregulation of the decoy death receptor, Dcr2, an established senescence marker that attenuates NK-mediated cell death. Accordingly, mice with defects in granule exocytosis accumulate senescent stellate cells and display more liver fibrosis in response to a fibrogenic agent. Our results thus provide new insights into the immune surveillance of senescent cells and reveal how granule exocytosis has a protective role against liver fibrosis.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell

organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
CSHL Authors:
Communities: CSHL Post Doctoral Fellows
CSHL labs > Lowe lab
Depositing User: Matt Covey
Date: 11 April 2013
Date Deposited: 23 May 2013 14:44
Last Modified: 23 May 2013 14:44
PMCID: PMC3630483
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28333

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