NKp44-NKp44 Ligand Interactions in the Regulation of Natural Killer Cells and Other Innate Lymphoid Cells in Humans

Monica Parodi, Herman Favoreel, Giovanni Candiano, Silvia Gaggero, Simona Sivori, Maria Cristina Mingari, Lorenzo Moretta, Massimo Vitale, Claudia Cantoni

Research output: Contribution to journalReview article

Abstract

Natural Killer (NK) cells are potent cytotoxic cells belonging to the family of Innate Lymphoid Cells (ILCs). Their most characterized effector functions are directed to the control of aberrant cells in the body, including both transformed and virus-infected cells. NK cell-mediated recognition of abnormal cells primarily occurs through receptor-ligand interactions, involving an array of inhibitory and activating NK receptors and different types of ligands expressed on target cells. While most of the receptors have become known over many years, their respective ligands were only defined later and their impressive complexity has only recently become evident. NKp44, a member of Natural Cytotoxicity Receptors (NCRs), is an activating receptor playing a crucial role in most functions exerted by activated NK cells and also by other NKp44+ immune cells. The large and heterogeneous panel of NKp44 ligands (NKp44L) now includes surface expressed glycoproteins and proteoglycans, nuclear proteins that can be exposed outside the cell, and molecules that can be either released in the extracellular space or carried in extracellular vesicles. Recent findings have extended our knowledge on the nature of NKp44L to soluble plasma glycoproteins, such as secreted growth factors or extracellular matrix (ECM)-derived glycoproteins. NKp44L are induced upon tumor transformation or viral infection but may also be expressed in normal cells and tissues. In addition, NKp44-NKp44L interactions are involved in the crosstalk between NK cells and different innate and adaptive immune cell types. NKp44 expression in different ILCs located in tissues further extends the potential role of NKp44-NKp44L interactions.

Original languageEnglish
Pages (from-to)719
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - Apr 9 2019

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Natural Killer Cells
Lymphocytes
Ligands
Glycoproteins
Membrane Glycoproteins
Extracellular Space
Virus Diseases
Proteoglycans
Nuclear Proteins
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Viruses
Neoplasms

Cite this

NKp44-NKp44 Ligand Interactions in the Regulation of Natural Killer Cells and Other Innate Lymphoid Cells in Humans. / Parodi, Monica; Favoreel, Herman; Candiano, Giovanni; Gaggero, Silvia; Sivori, Simona; Mingari, Maria Cristina; Moretta, Lorenzo; Vitale, Massimo; Cantoni, Claudia.

In: Frontiers in Immunology, Vol. 10, 09.04.2019, p. 719.

Research output: Contribution to journalReview article

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AU - Parodi, Monica

AU - Favoreel, Herman

AU - Candiano, Giovanni

AU - Gaggero, Silvia

AU - Sivori, Simona

AU - Mingari, Maria Cristina

AU - Moretta, Lorenzo

AU - Vitale, Massimo

AU - Cantoni, Claudia

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AB - Natural Killer (NK) cells are potent cytotoxic cells belonging to the family of Innate Lymphoid Cells (ILCs). Their most characterized effector functions are directed to the control of aberrant cells in the body, including both transformed and virus-infected cells. NK cell-mediated recognition of abnormal cells primarily occurs through receptor-ligand interactions, involving an array of inhibitory and activating NK receptors and different types of ligands expressed on target cells. While most of the receptors have become known over many years, their respective ligands were only defined later and their impressive complexity has only recently become evident. NKp44, a member of Natural Cytotoxicity Receptors (NCRs), is an activating receptor playing a crucial role in most functions exerted by activated NK cells and also by other NKp44+ immune cells. The large and heterogeneous panel of NKp44 ligands (NKp44L) now includes surface expressed glycoproteins and proteoglycans, nuclear proteins that can be exposed outside the cell, and molecules that can be either released in the extracellular space or carried in extracellular vesicles. Recent findings have extended our knowledge on the nature of NKp44L to soluble plasma glycoproteins, such as secreted growth factors or extracellular matrix (ECM)-derived glycoproteins. NKp44L are induced upon tumor transformation or viral infection but may also be expressed in normal cells and tissues. In addition, NKp44-NKp44L interactions are involved in the crosstalk between NK cells and different innate and adaptive immune cell types. NKp44 expression in different ILCs located in tissues further extends the potential role of NKp44-NKp44L interactions.

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