Perforin and granzymes: function, dysfunction and human pathology

Ilia Voskoboinik, James C Whisstock, Joseph A Trapani

Research output: Contribution to journalArticleResearchpeer-review

191 Citations (Scopus)

Abstract

A defining property of cytotoxic lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, but advances in structural and cellular biology have now begun to unravel how synergy between perforin and granzymes brings about target cell death. These and other advances are demonstrating the surprisingly broad pathophysiological roles of the perforin-granzyme pathway, and this has important implications for understanding immune homeostasis and for developing immunotherapies for cancer and other diseases. In particular, we are beginning to define and understand a range of human diseases that are associated with a failure to deliver active perforin to target cells. In this Review, we discuss the current understanding of the structural, cellular and clinical aspects of perforin and granzyme biology.
Original languageEnglish
Pages (from-to)388 - 400
Number of pages13
JournalNature Reviews Immunology
Volume15
Issue number6
DOIs
Publication statusPublished - 2015

Cite this

Voskoboinik, Ilia ; Whisstock, James C ; Trapani, Joseph A. / Perforin and granzymes: function, dysfunction and human pathology. In: Nature Reviews Immunology. 2015 ; Vol. 15, No. 6. pp. 388 - 400.
@article{5a9dd60d776f443dbc272c1ad4dd3131,
title = "Perforin and granzymes: function, dysfunction and human pathology",
abstract = "A defining property of cytotoxic lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, but advances in structural and cellular biology have now begun to unravel how synergy between perforin and granzymes brings about target cell death. These and other advances are demonstrating the surprisingly broad pathophysiological roles of the perforin-granzyme pathway, and this has important implications for understanding immune homeostasis and for developing immunotherapies for cancer and other diseases. In particular, we are beginning to define and understand a range of human diseases that are associated with a failure to deliver active perforin to target cells. In this Review, we discuss the current understanding of the structural, cellular and clinical aspects of perforin and granzyme biology.",
author = "Ilia Voskoboinik and Whisstock, {James C} and Trapani, {Joseph A}",
year = "2015",
doi = "10.1038/nri3839",
language = "English",
volume = "15",
pages = "388 -- 400",
journal = "Nature Reviews Immunology",
issn = "1474-1733",
publisher = "Nature Publishing Group",
number = "6",

}

Perforin and granzymes: function, dysfunction and human pathology. / Voskoboinik, Ilia; Whisstock, James C; Trapani, Joseph A.

In: Nature Reviews Immunology, Vol. 15, No. 6, 2015, p. 388 - 400.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Perforin and granzymes: function, dysfunction and human pathology

AU - Voskoboinik, Ilia

AU - Whisstock, James C

AU - Trapani, Joseph A

PY - 2015

Y1 - 2015

N2 - A defining property of cytotoxic lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, but advances in structural and cellular biology have now begun to unravel how synergy between perforin and granzymes brings about target cell death. These and other advances are demonstrating the surprisingly broad pathophysiological roles of the perforin-granzyme pathway, and this has important implications for understanding immune homeostasis and for developing immunotherapies for cancer and other diseases. In particular, we are beginning to define and understand a range of human diseases that are associated with a failure to deliver active perforin to target cells. In this Review, we discuss the current understanding of the structural, cellular and clinical aspects of perforin and granzyme biology.

AB - A defining property of cytotoxic lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, but advances in structural and cellular biology have now begun to unravel how synergy between perforin and granzymes brings about target cell death. These and other advances are demonstrating the surprisingly broad pathophysiological roles of the perforin-granzyme pathway, and this has important implications for understanding immune homeostasis and for developing immunotherapies for cancer and other diseases. In particular, we are beginning to define and understand a range of human diseases that are associated with a failure to deliver active perforin to target cells. In this Review, we discuss the current understanding of the structural, cellular and clinical aspects of perforin and granzyme biology.

UR - http://www.nature.com/nri/journal/v15/n6/full/nri3839.html

U2 - 10.1038/nri3839

DO - 10.1038/nri3839

M3 - Article

VL - 15

SP - 388

EP - 400

JO - Nature Reviews Immunology

JF - Nature Reviews Immunology

SN - 1474-1733

IS - 6

ER -