Transcriptome Profiling of IL-17A Preactivated Mesenchymal Stem Cells: A Comparative Study to Unmodified and IFN-γ Modified Mesenchymal Stem Cells.
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-gamma treated MSC (MSC-gamma), 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-gamma and UT-MSC and 67 genes between MSC-17 and UT-MSC. MSC-gamma were enriched for genes involved in immune response, antigen processing and presentation, humoral response, and complement activation, consistent with increased MSC-gamma immunogenicity. 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||Sivanathan, K. N.; Rojas-Canales, D.; Grey, S. T.; Gronthos, S.; Coates, P. T.|
|Responsible Garvan Author|
|Publisher Name||Stem Cells International|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/28293262|