TSG-6 secreted by human mesenchymal stromal cells downregulate type I interferon response in plasmacytoid dendritic cells and alleviates autoimmune nephritis in a murine model of systemic lupus erythematosus
Grant Data
Project Title
TSG-6 secreted by human mesenchymal stromal cells downregulate type I interferon response in plasmacytoid dendritic cells and alleviates autoimmune nephritis in a murine model of systemic lupus erythematosus
Principal Investigator
Dr Lee, Pamela Pui Wah
(Principal Investigator (PI))
Co-Investigator(s)
Professor Chan Godfrey Chi Fung
(Co-Investigator)
Duration
36
Start Date
2019-10-01
Completion Date
2022-09-30
Amount
1083952
Conference Title
TSG-6 secreted by human mesenchymal stromal cells downregulate type I interferon response in plasmacytoid dendritic cells and alleviates autoimmune nephritis in a murine model of systemic lupus erythematosus
Keywords
mesenchymal stromal cells, plasmacytoid dendritic cells, systemic lupus erythematosus, TSG-6, type I interferon
Discipline
Allergy/ImmunologyCell Biology
Panel
Biology and Medicine (M)
HKU Project Code
17122819
Grant Type
General Research Fund (GRF)
Funding Year
2019
Status
Completed
Objectives
1 To demonstrate TSG-6 mediates the immunosuppressive effect of mesenchymal stromal cells (MSCs) on plasmacytoid dendritic cells (pDC) upon TLR7 and TLR9 activation We hypothesize that MSCs can downregulate type-1 interferon signaling and cytokine production in pDC, in a TSG-6 dependent manner. This will be evaluated by comparing MSC with or without TSG-6 knockdown, and primary MSC with varied basal TSG-6 expression, on their effects on human pDC cell line or murine pDCs after TLR7 and TLR9 activation. 2 To evaluate the immunomodulation of TSG-6 and mesenchymal stromal cells (MSCs) on plasmacytoid dendritic cells (pDC) compartment in NZB/NZW F1 lupus mice and induced-lupus in TSG6-KO mice We hypothesize that TSG-6 and MSCs could suppress pDC activation and IFN-inducible gene expression after in vivo administration to lupus-prone mice, and such effect might be dependent on TSG-6. 3 To evaluate the effect of TSG-6 and mesenchymal stromal cells on interferon-inducible gene expression in kidneys and development of lupus nephritis in NZB/W F1 mice We hypothesize that TSG-6 and MSCs could modify the severity and progression of lupus nephritis and overall survival. We also hypothesize that TSG-6 and MSCs could downregulate type-1 interferon signature in renal tissues, which may contribute to less severe disease