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Siglec-7 expression is reduced on a natural killer (NK) cell subset of obese humans
Philip Rosenstock1,2, Rüdiger Horstkorte3, Vinayaga Srinivasan Gnanapragassam3
1Institute for Physiological Chemistry, Martin Luther University Halle-Wittenberg, Hollystraße 1, 06114, Halle (Saale), Germany. philip.rosenstock@uk-halle.de.
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/m2) and 11 obese (BMI > 30 kg/m2) 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. CD56bright 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 CD56bright 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 CD56bright and CD56dim, CD56bright NK cells had a higher amount of sialic acids on their surface compared to CD56dim NK cells regardless of body weight.
Insights
Obesity is linked to reduced Siglec-7 expression on natural killer (NK) cells, potentially indicating immune dysfunction. Sialic acid levels differ between NK cell types, irrespective of weight.
Area of Science:
- Immunology
- Cell Biology
- Metabolic Health
Background:
- Obesity alters adipocytokine profiles, impacting innate immune cell function.
- Natural killer (NK) cells are crucial for immune surveillance against tumors and viruses.
- Sialic acid-binding immunoglobulin-like lectins (Siglecs) are inhibitory receptors on NK cells.
Purpose of the Study:
- To compare the expression of Siglec-7, -9, and -10 on NK cells from normal weight and obese individuals.
- To investigate the role of sialic acid on NK cell surface in relation to body weight.
- To assess Siglec expression on NK cell lines.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were isolated from normal weight (BMI < 25 kg/m²) and obese (BMI > 30 kg/m²) donors.
- Flow cytometry was used to analyze Siglec expression on NK cell subsets (CD56bright and CD56dim).
- Fluorescently labeled lectins determined the amount of sialic acid on NK cells.
Main Results:
- No significant differences in immune cell percentages were observed between groups.
- Obese subjects showed reduced Siglec-7 expression on CD56bright NK cells compared to normal weight individuals.
- CD56bright NK cells exhibited higher surface sialic acid levels than CD56dim NK cells, independent of BMI.
Conclusions:
- Reduced Siglec-7 expression on CD56bright NK cells in obesity may signify impaired function.
- Siglec-7, -9, and -10 are not expressed on NK cell lines NK-92 and NKL.
- Sialic acid distribution on NK cell subsets is distinct and weight-independent.
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