title: Transcriptome Profiling of IL-17A Preactivated Mesenchymal Stem Cells: A Comparative Study to Unmodified and IFN-γModified Mesenchymal Stem Cells.
abstract: Human mesenchymal stem cells pretreatment with IL-17A (MSC-17) potently enhances T cell immunosuppression but not their immunogenicity, in addition to avidly promoting the induction of suppressive regulatory T cells. The aim of this study was to identify potential mechanisms by which human MSC-17 mediate their superior immunomodulatory function. Untreated-MSC (UT-MSC), IFN-γtreated MSC (MSC-γ), and MSC-17 were assessed for their gene expression profile by microarray. Significantly regulated genes were identified for their biological functions (Database for Annotation, Visualisation and Integrated Discovery, DAVID). Microarray analyses identified 1278 differentially regulated genes between MSC-γand UT-MSC and 67 genes between MSC-17 and UT-MSC. MSC-γwere enriched for genes involved in immune response, antigen processing and presentation, humoral response, and complement activation, consistent with increased MSC-γimmunogenicity. MSC-17 genes were associated with chemotaxis response, which may be involved in T cell recruitment for MSC-17 immunosuppression. MMP1, MMP13, and CXCL6 were highly and specifically expressed in MSC-17, which was further validated by real-time PCR. Thus, MMPs and chemokines may play a key role in mediating MSC-17 superior immunomodulatory function. MSC-17 represent a potential cellular therapy to suppress immunological T cell responses mediated by expression of an array of immunoregulatory molecules.
authors.affiliation: School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia; Centre for Clinical and Experimental Transplantation, Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: Kisha Nandini
authors.identifier: 0000-0002-2184-0565
authors.initials: KN
authors.lastname: Sivanathan
authors.affiliation: School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia; Centre for Clinical and Experimental Transplantation, Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: Darling
authors.initials: D
authors.lastname: Rojas-Canales
authors.affiliation: Transplantation Immunology Group, Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: Shane T
authors.initials: ST
authors.lastname: Grey
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, SA, Australia; Mesenchymal Stem Cell Laboratory, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Stan
authors.identifier: 0000-0002-6225-3084
authors.initials: S
authors.lastname: Gronthos
authors.affiliation: School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia; Centre for Clinical and Experimental Transplantation, Royal Adelaide Hospital, Adelaide, SA, Australia; Central Northern Adelaide Renal Transplantation Service, Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Coates