Mesenchymal stem/stroma cell (MSC)-derived nanoscale exosomes inhibit T cell proliferation by negative regulation of PI3K/Akt and MAPK/ERK pathway
نویسندگان
1 Department of Laboratory Sciences, Faculty of Paramedical Sciences, Kurdistan University of Medical Sciences (MUK), Sanandaj, Iran
2 Department of Biotechnology, Rajiv Gandhi Institute of IT and Biotechnology, Bharati Vidyapeeth University, Pune, India
3 Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4 Department of Internal Medicine and Rheumatology, Rheumatology Research Center , Tehran University of Medical Sciences, Tehran, Iran
5 Department of Surgery, Alborz University of Medical Sciences, Karaj, Alborz, Iran
6 Department of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
7 oxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
8 Department of Laboratory Sciences, Faculty of Paramedical Sciences, Hormozgan University of Medical Sciences (HUMS), Bandar Abbas, Iran
doi
10.22034/nmrj.2022.02.008چکیده
Objective(s): Exosomes, as membrane-enclosed nanovesicles (30–150 nm), transports active biomolecules between various cells. As natural nanoparticles (NP), they serve a key role in the diagnosis, treatment, as well as prevention of diseases. Recently it has been verified that MSC-derived exosomes are capable of adjusting immune cells' biological processes. We investigated the effects of the MSCs-derived exosome on T cell proliferation.Methods: xosomes isolated from the supernatant of bone marrow-MSC. The ultrastructure and shape of exosomes were evaluated via transmission electron microscopy (TEM), and CD9, CD63, and CD81 were detected by Western blotting. Then, we examined the effects of MSC-derived exosome on the proliferation of the T cells by MTT assay. Moreover, the expression levels of the PI3K, Akt, MAPK, and ERK were estimated at mRNA levels by Real-Time PCR. Results: We showed that MSCs-derived exosome inhibited T cell proliferation based on the MTT assay results. Real-time PCR analysis also exhibited that exosome co-culture resulted in down-regulation of PI3K, Akt, MAPK, and ERK expression levels.Conclusions: MSCs-derived exosome inhibits T cell proliferation by negative regulation of the survival- and proliferation-involved PI3K/Akt and MAPK/ERK pathway in vitro.
