SO075ADOPTIVE TRANSFER OF GINGIVA-DERIVED MESENCHYMAL STEM CELLS AMELIORATES LUPUS NEPHRITIS VIA INDUCTION OF CD4+HELIOS-FOXP3+ TREG THROUGH TARGETING OF CD39/CD73 SIGNALING PATHWAY

Abstract

Abstract Background and Aims Current approaches offer no cures for lupus nephritis. Accumulating evidence has revealed that manipulation of bone-marrow mesenchymal stem cells (BMSCs) may have the potential to treat lupus nephritis. While BMSC-based therapy faces many challenges such as limited cell availability, BMSCs from patients with autoimmune diseases are dysfunctional, use of BMSCs with long term has a potential risk on tumorigenesis and reduced clinical feasibility, we herein demonstrate that substitution of gingival-derived mesenchymal stem cells (GMSCs) results in significantly improved therapeutic effects on lupus-like disease model. Method Lupus-like disease has been induced with female New Zealand mixed (NZM) 2328 mice. In the study of prevention of lupus-like disease, GMSCs were injected i.v. into mice on age of 10 weeks. In some experiments, mice were injected with pre-treatment of GMSCs with CD39 or CD73 inhibitor. In the study of treatment of lupus-like disease, GMSCs were injected i.v. into mice on age of 20 weeks. Results In the study of prevention of lupus-like disease, infusion of GMSCs in NZM2328 mice significantly decreased the severity of lupus and kidney pathology scores, and down-regulated Th2, Tfh and Th17 cells. GMSCs significantly suppress activation and differentiation of B cells in vivo. Promotion of CD4+Helios- Foxp3+Treg cells following treatment with GMSCs, these increased Tregs were noted in spleen, LN and Kidney. Pre-treatment of GMSCs with CD39 or CD73 inhibitor significantly reversed the protective effect of GMSCs on lupus-like disease model. In the study of treatment of lupus-like disease, GMSCs can also treat the established disease. Conclusion The role of GMSCs in controlling lupus-like disease mostly depends upon CD39/CD73 signals and upon the induction of CD4+ Helios-Foxp3+Treg cells. GMSCs provide a promising approach for the treatment of lupus nephritis.