o:29820 Tungsten disulfide nanoparticles potentiate suppressive properties of human myeloid-derived suppressor cells in vitro Nanočestice volfram disulfida potenciraju supresivna svojstva humanih mijeloidnih supresora in vitro en ABSTRACT Myeloid derived suppressor cells (MDSCs) play a pivotal role in the regulation of immune response. Their targeted modulation by multifunctional nanoparticles opens new perspectives in theranostics of many diseases, including cancer and autoimmunity. Tungsten disulfide nanoparticles (WS2‐NPs) were shown to possess excellent optical properties and wide surface available for bioconjugation, making them ideal platform for novel theranostics. However, their biocompatibility and immunomodulatory properties, especially in interaction with MDSCs, are still unknown. To investigate this, here we used a model of human monocyte‐derived MDSCs‐like cells differentiated with GM‐CSF and IL‐6, which enables the differentiation of CD14+CD11b+HLA‐DRlow cells that are suppressive in co‐cultures with PHA‐stimulated PBMCs. According to side‐scatter parameter and microscope analyses, MDSCs displayed a high capacity to internalize WS2 nanoparticles in a dose‐dependent manner. Thereby, WS2‐NPs were not cytotoxic for MDSCs up to 100 μg/ml. However, WS2 (50 μg/ml) up‐regulated the expression of CD73, CD44 and Arginase‐1, and down‐regulated CD86 and CXCR4 expression by MDSCs, especially after additional challenge of the cells with LPS/IFN‐γ. WS2‐treated MDSCs, also produced less IL‐6 and TGF‐β compared to control MDSCs, irrespective of LPS/IFN‐γ stimulation. In co‐culture with PHA‐stimulated PBMCs, WS2‐ NPs potentiated the suppressive properties of MDSCs, which remained even after LPS/IFN‐γ challenge. Moreover, WS2‐treated MDSCs reduced IL‐17 and IFN‐γ levels in co‐cultures with PHA‐PBMCs, and increased the levels of IL‐10. These results suggest that WS2‐NPs are highly biocompatible and suitable for targeting MDSCs, particularly for their potentiating tolerogenic mechanisms, which could be exploited in designing new therapies in autoimmune and chronic inflammatory conditions. autoinflammation, drugs for immune modulation, myeloid derived suppressor cells 1552101 0014-2980 1552099 10.1002/eji.202170200 2023-05-25T19:23:08.437Z 44 yes 46 Karolina Janković Institute for Public Health of Serbia "Dr Milan Jovanović Batut", Belgrade, Serbia Marina Bekić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia person 0000-0002-6945-4241 Dušica Stojanović University of Belgrade, Faculty of Technology and Metallurgy, Department of Materials Science and Engineering, Serbia person Snežana Zečević University of East Sarajevo, Medical Faculty of Foča, Foča, Bosnia and Herzegovina person Nataša Ilić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia person Petar Uskoković University of Belgrade, Faculty of Technology and Metallurgy, Department of Materials Science and Engineering, Serbia person Miodrag Čolić University of East Sarajevo, Medical Faculty of Foča, Foča, Bosnia and Herzegovina person Sergej Tomić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia person 0000-0003-2570-1295 application/pdf 67732 https://phaidrabg.bg.ac.rs/o:29820 no yes 18 70 92000004 11A29 11A2904 11A41 European journal of immunology-Abstracts of ECI 2021 51 414 Wiley 2021