PI3k α and STAT 1 Interplay Regulates Human Mesenchymal Stem Cell Immune Polarization
作者: Marwan MounayarEirini KefaloyianniBrian SmithZhabiz SolhjouOmar H. MaaroufJamil AzziLola ChabtiniPaolo FiorinaMorey KrausRobert BriddellWilliam FodorAndreas HerrlichReza Abdi
作者单位: 1Transplantation Research Center Brigham and Women's and Children's Hospital Boston Massachusetts USA
2 Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA
3 Viacord LLC A PerkinElmer Company Cambridge Massachusetts USA
4 ViaCord Processing Lab ViaCord LLC A PerkinElmer Company Hebron Kentucky USA
5 The Cell Therapy Group Madison Connecticut USA
刊名: STEM CELLS, 2015, Vol.33 (6), pp.1892-1901
来源数据库: Wiley Journal
DOI: 10.1002/stem.1986
关键词: Mesenchymal stem cellsPI3K alphaSTAT1Interferon gammaCell signalingImmunosuppressionImmunotherapyT cells
原始语种摘要: Abstract(#br)The immunomodulatory capacity of mesenchymal stem cells (MSCs) is critical for their use in therapeutic applications. MSC response to specific inflammatory cues allows them to switch between a proinflammatory (MSC1) or anti‐inflammatory (MSC2) phenotype. Regulatory mechanisms controlling this switch remain to be defined. One characteristic feature of MSC2 is their ability to respond to IFNγ with induction of indoleamine 2,3‐dioxygenase (IDO), representing the key immunoregulatory molecule released by human MSC. Here, we show that STAT1 and PI3Kα pathways interplay regulates IFNγ‐induced IDO production in MSC. Chemical phosphoinositide 3‐kinase (PI3K) pan‐inhibition, PI3Kα‐specific inhibition or shRNA knockdown diminished IFNγ‐induced IDO production. This effect involved...
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