Date: Tuesday, June 14, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Human bone marrow derived MSC-17 are superior T cell immunomodulators for allotransplantation. Untreated-MSC (UT-MSC) or 5 days IFNγ (MSCγ) or IL-17A (MSC-17) treated MSC were assessed for T cell immunosuppression and ability to induce Tregs. Immunophenotype (flow cytometry) and gene expression profile (microarray) of 3 MSC donors were also analyzed. Significantly regulated genes (p<0.05, fold change (FC)<-2 or >2) were identified for their biological functions (Database for Annotation, Visualisation and Integrated Discovery, DAVID). MSC-17 potently suppressed PHA-induced T cell proliferation (3H-thymidine) and T cell activation (reduced CD25, IFNγ, TNFα, IL-2) by inducing Tregs expressing functional Treg markers (CD39, CD73, CD69, OX40, CTLA-4, GITR). Different to MSCγ, MSC-17 showed no upregulation of MHC or CD40 molecules. Microarray analyses identified 1278 differentially regulated genes (902 upregulated; 376 downregulated) between MSCγ and UT-MSC; and 67 genes (39 upregulated; 28 downregulated) between MSC-17 and UT-MSC. MSCγ were enriched for genes involved in immune response, antigen processing and presentation, humoral response and complement activation; consistent with increased MSCγ immunogenicity. MSC-17 genes were associated with chemotaxis response, which may be involved in T cell recruitment for MSC-17 immunosuppression. MSC are known to express MMP with chemotaxis and immunosuppressive properties. MMP13 was highly expressed specifically in MSC-17 (FC 15.6) and was validated by RT-PCR Hence, MMP13 may mediate the superior immunomodulatory function of MSC-17. MSC-17 represent a potential cellular therapy to suppress immunological T cell responses in allotransplantation, with minimal immunogenicity. Studies on the functional role of the key candidate molecule MMP13 in MSC-17 immunomodulation are currently underway.
CITATION INFORMATION: Sivanathan K, Rojas-Canales D, Gronthos S, Grey S, Coates P. IL-17A Preactivated Mesenchymal Stem Cells (MSC-17) Are Enriched for Genes Involved in T Cell Chemotaxis to Mediate Superior Immunosuppression. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Sivanathan K, Rojas-Canales D, Gronthos S, Grey S, Coates P. IL-17A Preactivated Mesenchymal Stem Cells (MSC-17) Are Enriched for Genes Involved in T Cell Chemotaxis to Mediate Superior Immunosuppression. [abstract]. Am J Transplant. 2016; 16 (suppl 3). http://atcmeetingabstracts.com/abstract/il-17a-preactivated-mesenchymal-stem-cells-msc-17-are-enriched-for-genes-involved-in-t-cell-chemotaxis-to-mediate-superior-immunosuppression/. Accessed September 21, 2017.
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