Mesenchymal Stromal Cell Secretion of Programmed Death-1 Ligands Regulates T Cell Mediated Immunosuppression

• DOI: 10.1002/stem.2509
• Publication Date: 2016-09-27T12:25:42Z
• Authors: Lindsay C. Davies; Nina Heldring; Nadir Kadri; Katarina Le Blanc
• Keywords: Immunosuppression

Abstract Mesenchymal stromal cells (MSCs) exert broad immunosuppressive potential, modulating the activity of innate and adaptive immune systems. As MSCs become accepted as a therapeutic option for treatment immunological disorders such Graft versus Host Disease, our need to understand intricate details by which they their effects is crucial. Programmed death-1 (PD-1) an important regulator in T cell activation homeostatic control. It has been reported that this pathway may be contact-dependent mediated immunomodulation MSCs. The aim study was establish whether MSCs, addition cell-surface expression, are able secrete PD-1 ligands (PD-L1 PD-L2) potential importance contact-independent mechanisms MSC immunosuppression. Here we report express PD-L1 PD-L2 regulated exposure interferon γ tumor necrosis factor α. via secretion ligands, suppress CD4+ cells, downregulate interleukin-2 induce irreversible hyporesponsiveness death. Suppressed demonstrated reduction AKT phosphorylation at T308 subsequent increase FOXO3 expression could reversed with blockade PD-L1. In conclusion, demonstrate first time, being known biological role These soluble factors play directly on behavior induction peripheral tolerance.