Interferon-c (IFN-c)-preactivated mesenchymal stem cells (MSC-c) are highly immunosuppressive but immunogenic in vivo due to their inherent expression of major histocompatibility (MHC) molecules. Here, we present an improved approach where we modified human bone marrowderived MSC with interleukin-17A (MSC-17) to enhance T cell immunosuppression but not their immunogenicity. MSC-17, unlike MSC-c, showed no induction or upregulation of MHC class I, MHC class II, and T cell costimulatory molecule CD40, but maintained normal MSC morphology and phenotypic marker expression. SIGNIFICANCE STATEMENTMesenchymal stem cells (MSC) are potent and promising immunomodulatory cell therapy that have progressed into the clinic for allotransplantation. Cytokine modified MSC show superior immunosuppressive properties compared to unmodified MSC. In this study, we describe the enhanced immunosuppressive properties of MSC generated under the influence of the proinflammatory cytokine interleukin-17A (MSC-17) compared to interferon-gamma pre-treated MSC (MSC-c). Specifically these human MSC-17 have translational potential in transplantation protocols because they do not express MHC class II, thereby reducing their immunogenicity, in addition to avidly promote the formation of induced T regulatory cells.

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