IFN-γ orchestrates mesenchymal stem cell plasticity through the signal transducer and activator of transcription 1 and 3 and mammalian target of rapamycin pathways

摘要: Background Mesenchymal stem cells (MSCs) display a therapeutic plasticity because of their ability to modulate immunity, foster tissue repair, and differentiate into mesodermal cells. IFN-γ has been described differently affect human mesenchymal cell (hMSC) mouse (mMSC) immunomodulation differentiation, depending on the inflammatory milieu. Objective We aimed at dissecting relevant intracellular pathways through which affects MSC consequence manipulation functions. Methods Modification IFN-γ–dependent in mMSCs was carried out in vitro gene silencing or chemical inhibition key components. Functional outcomes were assessed by means Western blotting, real-time PCR, proliferation assays MSCs. The effect T cells addressed T-cell assays; mammalian target rapamycin (mTOR) MSCs studied in vivo model delayed-type hypersensitivity assay. To address whether similar mechanisms are involved also hMSCs stimulation, same final outcome immunomodulatory properties evaluated based PCR proliferation. Results revealed that IFN-γ–induced immunoregulation is mediated early phosphorylation signal transducer activator transcription (STAT) 1 STAT3, significantly enhanced an extracellular signal-regulated kinase 1/2–dependent mTOR inhibition, thereby promoting pSTAT1 nuclear translocation. Accordingly, after augmented inhibit control . Similarly, blockade, immunoregulatory features. A sustained exposure led STAT3 activity, resulted impaired differentiation. Conclusion These results provide new insights about affected IFN-γ, demonstrating pharmacologic genetic can enhance functions, could be translated novel approaches.