Down-Regulation of MHC II in Mesenchymal Stem Cells at High IFN-γ Can Be Partly Explained by Cytoplasmic Retention of CIITA

摘要: Mesenchymal stem cells (MSCs) are located in postnatal bone marrow, show plasticity, linked to various marrow disorders, exhibit phagocytosis, exert Ag-presenting properties (APC), and immune suppressive. Unlike professional APCs, MSCs respond bimodally IFN-γ MHC-II expression, with expression at 10 U/ml baseline, down-regulation 100 U/ml. The effects high could not be explained by of its receptor, IFN-γRI. In this study, we report on the mechanisms which regulates MSCs. Gel shift assay Western blot analyses showed dose-dependent increases activated STAT-1, indicating responsiveness blots decreased intracellular MHC-II, transcription master regulator CIITA, based RT-PCR situ immunofluorescence. Reporter gene assays PIII PIV CIITA promoters indicate constitutive a switch IFN-γ, presence factors for effect promoter responses. We level because protein was observed cytosol nuclei level. proline/serine/threonine region significant decrease phosphorylation levels. An understanding bimodal provide insights homeostasis, extrapolated MSC dysfunction hematological disorders.