IL-17A Preactivated Mesenchymal Stem Cells (MSC-17) Are Enriched for Genes Involved in T Cell Chemotaxis to Mediate Superior Immunosuppression.
1School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia
2Centre for Clinical and Experimental Transplantation, Royal Adelaide Hospital, Adelaide, South Australia, Australia
3Centre for Stem Cell Research and Robinson Institute, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
4Mesenchymal Stem Cell Laboratory, School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia
5Transplant Immunology Group, Garvin Institute of Medical Research, Sydney, New South Wales, Australia.
Meeting: 2016 American Transplant Congress
Abstract number: D54
Keywords: Gene expression, Immunosuppression, Stem cells, T cells
Session Information
Session Name: Poster Session D: Chimerism/Stem Cells, Cellular/Islet Transplantation, Innate Immunity, Chronic Rejection
Session Type: Poster Session
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). https://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 May 8, 2025.« Back to 2016 American Transplant Congress