Natural cytotoxicity receptors

Broader expression patterns and functions in innate and adaptive immune cells

Kelly Hudspeth, Bruno Silva-Santos, Domenico Mavilio

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Natural cytotoxicity receptors (NCRs) have been classically defined as activating receptors delivering potent signals to Natural Killer (NK) cells in order to lyze harmful cells and to produce inflammatory cytokines. Indeed, the elicitation of NK cell effector functions after engagement of NCRs with their ligands on tumor or virus infected cells without the need for prior antigen recognition is one of the main mechanisms that allow a rapid clearance of target cells.The three known NCRs, NKp46, NKp44, and NKp30, comprise a family of germline encoded Ig-like trans-membrane (TM) receptors. Until recently, NCRs were thought to be NK cell specific surface molecules, thus making it possible to easily distinguish NK cells from phenotypically similar cell types. Moreover, it has also been found that the surface expression of NKp46 is conserved on NK cells across mammalian species. This discovery allowed for the use of NKp46 as a reliable marker to identify NK cells in different animal models, a comparison that was not possible before due to the lack of a common and comprehensive receptor repertoire between different species. However, several studies over the recent few years indicated that NCR expression is not exclusively confined to NK cells, but is also present on populations of T as well as of NK-like lymphocytes. These insights raised the hypothesis that the induced expression of NCRs on certain T cell subsets is governed by defined mechanisms involving the engagement of the T cell receptor (TCR) and the action of pro-inflammatory cytokines. In turn, the acquisition of NCRs by T cell subsets is also associated with a functional independence of these Ig-like TM receptors from TCR signaling. Here, we review these novel findings with respect to NCR-mediated functions of NK cells and we also discuss the functional consequences of NCR expression on non-NK cells, with a particular focus on the T cell compartment.

Original languageEnglish
Article numberArticle 69
JournalFrontiers in Immunology
Volume4
Issue numberMAR
DOIs
Publication statusPublished - 2013

Fingerprint

Natural Killer Cells
T-Lymphocyte Subsets
T-Cell Antigen Receptor
Natural Cytotoxicity Triggering Receptor 2
Natural Cytotoxicity Triggering Receptor 3
Natural Cytotoxicity Triggering Receptor 1
Cytokines
Oncogenic Viruses
Membranes
Animal Models
Lymphocytes
Ligands
T-Lymphocytes
Antigens
Population

Keywords

  • Activation
  • Homeostasis
  • Mucosal immunity
  • Ncrs
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Natural cytotoxicity receptors : Broader expression patterns and functions in innate and adaptive immune cells. / Hudspeth, Kelly; Silva-Santos, Bruno; Mavilio, Domenico.

In: Frontiers in Immunology, Vol. 4, No. MAR, Article 69, 2013.

Research output: Contribution to journalArticle

@article{ce7ec743a31f4ab98558cba5f8b802ad,
title = "Natural cytotoxicity receptors: Broader expression patterns and functions in innate and adaptive immune cells",
abstract = "Natural cytotoxicity receptors (NCRs) have been classically defined as activating receptors delivering potent signals to Natural Killer (NK) cells in order to lyze harmful cells and to produce inflammatory cytokines. Indeed, the elicitation of NK cell effector functions after engagement of NCRs with their ligands on tumor or virus infected cells without the need for prior antigen recognition is one of the main mechanisms that allow a rapid clearance of target cells.The three known NCRs, NKp46, NKp44, and NKp30, comprise a family of germline encoded Ig-like trans-membrane (TM) receptors. Until recently, NCRs were thought to be NK cell specific surface molecules, thus making it possible to easily distinguish NK cells from phenotypically similar cell types. Moreover, it has also been found that the surface expression of NKp46 is conserved on NK cells across mammalian species. This discovery allowed for the use of NKp46 as a reliable marker to identify NK cells in different animal models, a comparison that was not possible before due to the lack of a common and comprehensive receptor repertoire between different species. However, several studies over the recent few years indicated that NCR expression is not exclusively confined to NK cells, but is also present on populations of T as well as of NK-like lymphocytes. These insights raised the hypothesis that the induced expression of NCRs on certain T cell subsets is governed by defined mechanisms involving the engagement of the T cell receptor (TCR) and the action of pro-inflammatory cytokines. In turn, the acquisition of NCRs by T cell subsets is also associated with a functional independence of these Ig-like TM receptors from TCR signaling. Here, we review these novel findings with respect to NCR-mediated functions of NK cells and we also discuss the functional consequences of NCR expression on non-NK cells, with a particular focus on the T cell compartment.",
keywords = "Activation, Homeostasis, Mucosal immunity, Ncrs, T cells",
author = "Kelly Hudspeth and Bruno Silva-Santos and Domenico Mavilio",
year = "2013",
doi = "10.3389/fimmu.2013.00069",
language = "English",
volume = "4",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S.A.",
number = "MAR",

}

TY - JOUR

T1 - Natural cytotoxicity receptors

T2 - Broader expression patterns and functions in innate and adaptive immune cells

AU - Hudspeth, Kelly

AU - Silva-Santos, Bruno

AU - Mavilio, Domenico

PY - 2013

Y1 - 2013

N2 - Natural cytotoxicity receptors (NCRs) have been classically defined as activating receptors delivering potent signals to Natural Killer (NK) cells in order to lyze harmful cells and to produce inflammatory cytokines. Indeed, the elicitation of NK cell effector functions after engagement of NCRs with their ligands on tumor or virus infected cells without the need for prior antigen recognition is one of the main mechanisms that allow a rapid clearance of target cells.The three known NCRs, NKp46, NKp44, and NKp30, comprise a family of germline encoded Ig-like trans-membrane (TM) receptors. Until recently, NCRs were thought to be NK cell specific surface molecules, thus making it possible to easily distinguish NK cells from phenotypically similar cell types. Moreover, it has also been found that the surface expression of NKp46 is conserved on NK cells across mammalian species. This discovery allowed for the use of NKp46 as a reliable marker to identify NK cells in different animal models, a comparison that was not possible before due to the lack of a common and comprehensive receptor repertoire between different species. However, several studies over the recent few years indicated that NCR expression is not exclusively confined to NK cells, but is also present on populations of T as well as of NK-like lymphocytes. These insights raised the hypothesis that the induced expression of NCRs on certain T cell subsets is governed by defined mechanisms involving the engagement of the T cell receptor (TCR) and the action of pro-inflammatory cytokines. In turn, the acquisition of NCRs by T cell subsets is also associated with a functional independence of these Ig-like TM receptors from TCR signaling. Here, we review these novel findings with respect to NCR-mediated functions of NK cells and we also discuss the functional consequences of NCR expression on non-NK cells, with a particular focus on the T cell compartment.

AB - Natural cytotoxicity receptors (NCRs) have been classically defined as activating receptors delivering potent signals to Natural Killer (NK) cells in order to lyze harmful cells and to produce inflammatory cytokines. Indeed, the elicitation of NK cell effector functions after engagement of NCRs with their ligands on tumor or virus infected cells without the need for prior antigen recognition is one of the main mechanisms that allow a rapid clearance of target cells.The three known NCRs, NKp46, NKp44, and NKp30, comprise a family of germline encoded Ig-like trans-membrane (TM) receptors. Until recently, NCRs were thought to be NK cell specific surface molecules, thus making it possible to easily distinguish NK cells from phenotypically similar cell types. Moreover, it has also been found that the surface expression of NKp46 is conserved on NK cells across mammalian species. This discovery allowed for the use of NKp46 as a reliable marker to identify NK cells in different animal models, a comparison that was not possible before due to the lack of a common and comprehensive receptor repertoire between different species. However, several studies over the recent few years indicated that NCR expression is not exclusively confined to NK cells, but is also present on populations of T as well as of NK-like lymphocytes. These insights raised the hypothesis that the induced expression of NCRs on certain T cell subsets is governed by defined mechanisms involving the engagement of the T cell receptor (TCR) and the action of pro-inflammatory cytokines. In turn, the acquisition of NCRs by T cell subsets is also associated with a functional independence of these Ig-like TM receptors from TCR signaling. Here, we review these novel findings with respect to NCR-mediated functions of NK cells and we also discuss the functional consequences of NCR expression on non-NK cells, with a particular focus on the T cell compartment.

KW - Activation

KW - Homeostasis

KW - Mucosal immunity

KW - Ncrs

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=84877044329&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877044329&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2013.00069

DO - 10.3389/fimmu.2013.00069

M3 - Article

VL - 4

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - MAR

M1 - Article 69

ER -