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Special Issue "Advances in NK Cell Receptors and Their Ligands"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 July 2019).

Special Issue Editors

Guest Editor
Prof. Rossella Paolini Website E-Mail
Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, Viale Regina Elena 291, 00161 Rome, Italy
Interests: innate immunity; natural killer (NK) cells; immune receptors; signal transduction; post-translational modification; endocytosis
Guest Editor
Dr. Rosa Molfetta Website E-Mail
Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, Viale Regina Elena 291, 00161 Rome, Italy
Interests: innate immunity; innate receptor signaling; post-translational regulation; ubiquitination; receptor endocytosis

Special Issue Information

Dear Colleagues,

Natural killer (NK) cells are a subset of highly sophisticated innate lymphocytes endowed with a potent and rapid cytotoxicity against infected and transformed cells and the capability to release cytokine and chemokine with immunomodulatory functions. Over the past two decades, new insights into NK cell functions in immune surveillance has been provided by our understanding of what and how NK cell “see” a potential target cell. Recognition by NK cells involves the action of several distinct receptors for Major Hystocompatibility class I molecules (MHC-I) able to simultaneuosly deliver activating and inhibitory signals whose balance determine the functional outcome. Inhibitory receptors prevent NK cells from killing healthy cells by MHC-I ligand recognition, while activating receptors bind to MHC-I related ligands specifically induced or up-regulated on damaged cells promoting their lysis. However, transformed and infected cells can evade recognition and destruction by NK cells through the down-modulation of activating ligands and the up-regulation of ligands for inhibitory receptors. Furthermore, down-modulation of NK cell receptors, often occurring upon engagement by their respective ligands, can contribute to impair the ability of NK cells to eliminate dangerous cells.

This Special Issue welcome submissions of research articles or reviews focused on: 1) receptors acquired during NK cell development; 2) receptors express on different NK cell subsets; 3) signals initiated by activating and inhibitory NK cell receptors; 4) molecular mechanisms regulating expression of NK cell receptors and their ligands in transformed and infected cells.

Prof. Rossella Paolini
Dr. Rosa Molfetta
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Natural killer (NK) cells
  • NK cell activating/inhibitory receptors
  • NK cell ligands
  • NK cell receptor-mediated signaling

Published Papers (3 papers)

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Review

Open AccessReview
Potential of the NKG2D/NKG2DL Axis in NK Cell-Mediated Clearance of the HIV-1 Reservoir
Int. J. Mol. Sci. 2019, 20(18), 4490; https://doi.org/10.3390/ijms20184490 - 11 Sep 2019
Abstract
Viral persistency in latently infected CD4+ T cells despite antiretroviral therapy (ART) represents a major drawback in the fight against HIV-1. Efforts to purge latent HIV-1 have been attempted using latency reversing agents (LRAs) that activate expression of the quiescent virus. However, [...] Read more.
Viral persistency in latently infected CD4+ T cells despite antiretroviral therapy (ART) represents a major drawback in the fight against HIV-1. Efforts to purge latent HIV-1 have been attempted using latency reversing agents (LRAs) that activate expression of the quiescent virus. However, initial trials have shown that immune responses of ART-treated patients are ineffective at clearing LRA-reactivated HIV-1 reservoirs, suggesting that an adjuvant immunotherapy is needed. Here we overview multiple lines of evidence indicating that natural killer (NK) cells have the potential to induce anti-HIV-1 responses relevant for virus eradication. In particular, we focus on the role of the NKG2D activating receptor that crucially enables NK cell-mediated killing of HIV-1-infected cells. We describe recent data indicating that LRAs can synergize with HIV-1 at upregulating ligands for NKG2D (NKG2DLs), hence sensitizing T cells that exit from viral latency for recognition and lysis by NK cells; in addition, we report in vivo and ex vivo data showing the potential benefits and drawbacks that LRAs may have on NKG2D expression and, more in general, on the cytotoxicity of NK cells. Finally, we discuss how the NKG2D/NKG2DLs axis can be exploited for the development of effective HIV-1 eradication strategies combining LRA-induced virus reactivation with recently optimized NK cell-based immunotherapies. Full article
(This article belongs to the Special Issue Advances in NK Cell Receptors and Their Ligands)
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Open AccessReview
DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?
Int. J. Mol. Sci. 2019, 20(15), 3715; https://doi.org/10.3390/ijms20153715 - 30 Jul 2019
Abstract
Natural Killer (NK) cells play a critical role in host defense against viral infections. The mechanisms of recognition and killing of virus-infected cells mediated by NK cells are still only partially defined. Several viruses induce, on the surface of target cells, the expression [...] Read more.
Natural Killer (NK) cells play a critical role in host defense against viral infections. The mechanisms of recognition and killing of virus-infected cells mediated by NK cells are still only partially defined. Several viruses induce, on the surface of target cells, the expression of molecules that are specifically recognized by NK cell-activating receptors. The main NK cell-activating receptors involved in the recognition and killing of virus-infected cells are NKG2D and DNAM-1. In particular, ligands for DNAM-1 are nectin/nectin-like molecules involved also in mechanisms allowing viral infection. Viruses adopt several immune evasion strategies, including those affecting NK cell-mediated immune surveillance, causing persistent viral infection and the development of virus-associated diseases. The virus’s immune evasion efficacy depends on molecules differently expressed during the various phases of infection. In this review, we overview the molecular strategies adopted by viruses, specifically cytomegalovirus (CMV), human immunodeficiency virus (HIV-1), herpes virus (HSV), Epstein-Barr virus (EBV) and hepatitis C virus (HCV), aiming to evade NK cell-mediated surveillance, with a special focus on the modulation of DNAM-1 activating receptor and its ligands in various phases of the viral life cycle. The increasing understanding of mechanisms involved in the modulation of activating ligands, together with those mediating the viral immune evasion strategies, would provide critical tools leading to design novel NK cell-based immunotherapies aiming at viral infection control, thus improving cure strategies of virus-associated diseases. Full article
(This article belongs to the Special Issue Advances in NK Cell Receptors and Their Ligands)
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Open AccessReview
Advanced Materials and Devices for the Regulation and Study of NK Cells
Int. J. Mol. Sci. 2019, 20(3), 646; https://doi.org/10.3390/ijms20030646 - 02 Feb 2019
Abstract
Natural Killer (NK) cells are innate lymphocytes that contribute to immune protection by cytosis, cytokine secretion, and regulation of adaptive responses of T cells. NK cells distinguish between healthy and ill cells, and generate a cytotoxic response, being cumulatively regulated by environmental signals [...] Read more.
Natural Killer (NK) cells are innate lymphocytes that contribute to immune protection by cytosis, cytokine secretion, and regulation of adaptive responses of T cells. NK cells distinguish between healthy and ill cells, and generate a cytotoxic response, being cumulatively regulated by environmental signals delivered through their diverse receptors. Recent advances in biomaterials and device engineering paved the way to numerous artificial microenvironments for cells, which produce synthetic signals identical or similar to those provided by the physiological environment. In this paper, we review recent advances in materials and devices for artificial signaling, which have been applied to regulate NK cells, and systematically study the role of these signals in NK cell function. Full article
(This article belongs to the Special Issue Advances in NK Cell Receptors and Their Ligands)
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