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      Siglec-7 expression is reduced on a natural killer (NK) cell subset of obese humans

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          Abstract

          Obesity leads to an altered adipocytokine production negatively effecting the function of natural killer cells (NK cells), which are important effector cells of the innate immune system. NK cells provide a defence against tumour cells or virus infected cells and have different activating and inhibitory surface receptors to distinguish between normal and transformed cells. One group of the inhibitory receptors are the sialic acid-binding immunoglobulin-like lectins (Siglecs). The aim of this study was to compare the expression of Siglecs-7, -9 and -10 on NK cells from normal weight and obese subjects. Therefore peripheral blood mononuclear cells (PBMC) were isolated from 10 normal weight (BMI < 25 kg/m 2) and 11 obese (BMI > 30 kg/m 2) blood donors and analysed by flow cytometry. Moreover, the amount of sialic acid on NK cell was determined using a fluorescent labelled lectin that binds terminal sialic acids. Percentages of immune cells were not altered between normal weight and obese individuals. CD56 bright NK cells from obese subjects had a reduced expression of Siglec-7 while the expression of Siglec-9 was not altered. The reduction of Siglec-7 expression on CD56 bright NK cells might be a marker for their dysfunction. Moreover, Siglecs-7, -9 and -10 are not expressed on the NK cell lines NK-92 and NKL. When comparing the two NK cell subpopulations CD56 bright and CD56 dim, CD56 bright NK cells had a higher amount of sialic acids on their surface compared to CD56 dim NK cells regardless of body weight.

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          CD56bright natural killer (NK) cells: an important NK cell subset.

          Human natural killer (NK) cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56. The two major subsets are CD56(bright) CD16(dim/) (-) and CD56(dim) CD16(+), respectively. In this review, we will focus on the CD56(bright) NK cell subset. These cells are numerically in the minority in peripheral blood but constitute the majority of NK cells in secondary lymphoid tissues. They are abundant cytokine producers but are only weakly cytotoxic before activation. Recent data suggest that under certain conditions, they have immunoregulatory properties, and that they are probably immediate precursors of CD56(dim) NK cells. CD56(bright) NK cell percentages are expanded or reduced in a certain number of diseases, but the significance of these variations is not yet clear.
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            Activating and inhibitory receptors of natural killer cells.

            Natural killer (NK) cells are potent immune effector cells that can respond to infection and cancer, as well as allowing maternal adaptation to pregnancy. In response to malignant transformation or pathogenic invasion, NK cells can secrete cytokine and may be directly cytolytic, as well as exerting effects indirectly through other cells of the immune system. To recognize and respond to inflamed or infected tissues, NK cells express a variety of activating and inhibitory receptors including NKG2D, Ly49 or KIR, CD94-NKG2 heterodimers and natural cytotoxicity receptors, as well as co-stimulatory receptors. These receptors recognize cellular stress ligands as well as major histocompatibility complex class I and related molecules, which can lead to NK cell responses. Importantly, NK cells must remain tolerant of healthy tissue, and some of these receptors can also prevent activation of NK cells. In this review, we describe the expression of prominent NK cell receptors, as well as expression of their ligands and their role in immune responses. In addition, we describe the main signaling pathways used by NK cell receptors. Although we now appreciate that NK cell biology is more complicated than first thought, there are still facets of their biology that remain unclear. These will be highlighted and discussed in this review.
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              Human natural killer cell development and biology.

              Natural killer cells are important innate immune effector cells with potentially broad applications in the treatment of human malignancy due to their ability to lyse neoplastic cells without the need for tumor-specific antigen recognition. Human NK cells can be divided into two functional subsets based on their surface expression of CD56; CD56(bright) immunoregulatory cells and CD56(dim) cytotoxic cells. In addition to functional differences, these NK cell subsets can be modulated differently by interleukin (IL)-2, which has permitted the development of lower dose, better tolerated IL-2 regimens for the in vivo expansion and activation of NK cells. The importance of early hematopoietic growth factors, such as c-kit ligand and flt-3 ligand, and their synergy with IL-15 in the development of human NK cells in the bone marrow has permitted the investigation of novel cytokine combinations for optimizing in vivo expansion of NK cell in the clinic. The importance of lymph nodes as a site for NK cell development has recently been elucidated. Furthermore, progress in the field of how NK cell recognize target cells via activating and inhibitory receptors, and how the balance of signals from these receptors can modulate NK cell activity has revolutionized our understanding of the selective killing of tumor cells by NK cells while sparing normal cells. In this review, we summarize current understanding of NK cell biology, and highlight how such knowledge may be translated to optimize the efficacy of using autologous or allogeneic NK cell for the immunotherapy of cancer.
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                Author and article information

                Contributors
                philip.rosenstock@uk-halle.de
                Journal
                Immunol Res
                Immunol. Res
                Immunologic Research
                Springer US (New York )
                0257-277X
                1559-0755
                7 August 2017
                7 August 2017
                2017
                : 65
                : 5
                : 1017-1024
                Affiliations
                [1 ]ISNI 0000 0001 0679 2801, GRID grid.9018.0, Institute for Physiological Chemistry, , Martin Luther University Halle-Wittenberg, ; Hollystraße 1, 06114 Halle (Saale), Germany
                [2 ]ISNI 0000 0001 0679 2801, GRID grid.9018.0, Department of Anatomy and Cell Biology, , Martin Luther University Halle-Wittenberg, ; Grosse Steinstrasse 52 1, 06108 Halle (Saale), Germany
                [3 ]ISNI 0000 0004 0390 1701, GRID grid.461820.9, Department of Transfusion Medicine, , University Hospital Halle (Saale), ; Ernst-Grube-Straße 40, 06097 Halle (Saale), Germany
                Author information
                http://orcid.org/0000-0002-1300-505X
                Article
                8942
                10.1007/s12026-017-8942-y
                5613057
                28786023
                aa61946d-1e1e-41fb-b009-65a95ed785de
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Funding
                Funded by: RTG 2155 (ProMoAge)
                Categories
                Original Article
                Custom metadata
                © Springer Science+Business Media, LLC 2017

                cd56,facs analysis,nk-cells,obesity,sialic acids,siglec
                cd56, facs analysis, nk-cells, obesity, sialic acids, siglec

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