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W4313408040 abstract "Abstract Mesenchymal stem cells (MSCs) are well-known for their immunomodulatory functions in innate and adaptive immunity. Their functional diversity was verified in various disease model through paracrine mechanisms. MSCs-derived secretome consists of a variety of bioactive components such as nucleic acids, cytokines, chemokines, and small molecules. However, the effect of MSCs on natural killer (NK) cells activity is still controversial. In this study, we tried to identify active components within MSCs secretome possessing ability to affect NK cells activity and to investigate their action mechanisms. We found that MSCs secretome had no effect on survival and proliferation of NK-92 cells but specifically diminished cell activity, as evidenced by lower secretion of cytotoxic granules and effector cytokines and also reducing killing ability. This effect was reproduced in human peripheral NK cells equally. Moreover, seven candidates for modulating inflammation within MSCs secretome were identified via LC-MS/MS proteomic analysis. Interestingly, they are totally different factors from those known as MSC’s immunomodulatory factor. After treatment of neutralizing antibodies to each candidate, we observed that only three of the groups with neutralizing antibodies recovered cytokine secretion and cytotoxic ability of NK-92 cells. These findings suggest that MSCs secretome can inhibit the effector functions of NK cells via some particular molecules, which are increasing expression of inhibitory receptor CD96 on NK cells, consequently activating inhibitory signal. This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. 2021R1F1A1049630)." @default.
W4313408040 created "2023-01-06" @default.
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W4313408040 date "2022-05-01" @default.
W4313408040 modified "2023-09-26" @default.
W4313408040 title "Several active components within MSCs secretome inhibit the IL-2-mediated effector functions of NK cells" @default.
W4313408040 doi "https://doi.org/10.4049/jimmunol.208.supp.165.13" @default.
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