Pende D, Castriconi R, Romagnani P, Spaggiari GM, Marcenaro S, Dondero A et al.. Expression of the DNAM-1 ligands, Nectin-2 (CD112) and poliovirus receptor (CD155), on dendritic cells: relevance for natural killer-dendritic cell interaction. Blood 107: 2030-2036

University of Florence, Florens, Tuscany, Italy
Blood (Impact Factor: 10.45). 04/2006; 107(5):2030-6. DOI: 10.1182/blood-2005-07-2696
Source: PubMed


In this study, we demonstrate the involvement of DNAM-1-triggering receptor and its ligands, poliovirus receptor (PVR) and Nectin-2, in natural killer (NK) cell-mediated lysis of dendritic cells (DCs). The surface expression of both ligands was up-regulated in DCs as compared to monocytes. It reached maximal densities after DC maturation induced by different stimuli including lipopolysaccharide (LPS), poly I:C, flagellin, and CD40L. Both immunohistochemical analysis and confocal microscopy revealed expression of DNAM-1 ligands by DCs in lymph nodes in which they were localized in the parafollicular T-cell region and surrounded the high endothelial venules. Remarkably, in cytolytic assays, DNAM-1 cooperated with NKp30 in the NK-mediated killing of both immature and mature DCs and the degree of contribution of DNAM-1 appeared to correlate with the surface densities of its specific ligands PVR and Nectin-2.

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    • "We can speculate that cellular interactions and signals provided to DNAM-1 À and DNAM-1 + NK cells might be different, ultimately leading to functional divergence. Indeed, DNAM-1 at the cell surface of lymphocytes constantly interacts with its ligands expressed on DCs (Seth et al., 2011), and the absence of this receptor has been shown to negatively impact NK cell and DC crosstalk (Pende et al., 2006; Ramsbottom et al., 2014; Shibuya et al., 1996). The absence of DNAM-1 on NK cells may therefore limit their access to homeostatic DC-derived signals including IL-15 (Lucas et al., 2007). "
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    ABSTRACT: Natural killer (NK) cells comprise a heterogeneous population of cells important for pathogen defense and cancer surveillance. However, the functional significance of this diversity is not fully understood. Here, we demonstrate through transcriptional profiling and functional studies that the activating receptor DNAM-1 (CD226) identifies two distinct NK cell functional subsets: DNAM-1(+) and DNAM-1(-) NK cells. DNAM-1(+) NK cells produce high levels of inflammatory cytokines, have enhanced interleukin 15 signaling, and proliferate vigorously. By contrast, DNAM-1(-) NK cells that differentiate from DNAM-1(+) NK cells have greater expression of NK-cell-receptor-related genes and are higher producers of MIP1 chemokines. Collectively, our data reveal the existence of a functional program of NK cell maturation marked by DNAM-1 expression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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    • "NK cells are presently known to represent long-lived innate cells, whose functional spectrum extends beyond classical search-and-destroy patrolling activity and/or early recruitment of immune responses. NK cell function indeed also includes regulation of other innate and adaptive functions through their direct or indirect reciprocal interaction (crosstalk) with macrophages, polymorphonuclear cells (6, 7), fibroblasts (8), DC (9–11), and T cells. "
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    • "Moreover, modulation of PVR surface expression might occur during infections. Different pathogen-derived stimuli such as LPS, poly I:C, and flagellin upregulated the surface expression of PVR (and nectin-2) in human DC (54) and in murine antigen-presenting cells (55) via the MYD88 and TRIF pathways. It has also been shown that expression of the human immunodeficiency virus type 1 (HIV-1) Vpr protein increases PVR levels in Jurkat T cells. "
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