Center for Craniofacial Molecular Biology, Tyk2 list University of Southern California, Keck College
Center for Craniofacial Molecular Biology, University of Southern California, Keck College of Medicine, Los Angeles, CA. 90033, USA of Surgery, Initially affiliated Hospital of Shantou University, Shantou, 515041 China Service, Veterans Affairs Health-related Center, Memphis; TN. 38104, USA4Division5Research6UMR6218,Molecular Immunology, University and CNRS, 3b rue de la Ferollerie, Orleans. 45071, France of Immunology, Shanghai East Hospital at Tongji University, Shanghai, 200120, China7InstituteAbstractObjective–Current approaches present no cures for rheumatoid arthritis (RA). Accumulating evidence has revealed that manipulation of bone-marrow mesenchymal stem cells (BMSCs) may possibly have the potential to treat RA. When BMSC-based therapy faces quite a few challenges like restricted cell availability and lowered clinical feasibility, we herein demonstrate that substitution of gingival-derived mesenchymal stem cells (GMSCs) results in considerably enhanced therapeutic effects on established collagen-induced arthritis (CIA).*Address correspondence and reprint requests to Song Guo Zheng, MD, PhD, Division of Rheumatology and Immunology, University of Southern California, 2011 Zonal Avenue, HMR 711, Los Angeles, CA 90033. [email protected]. Telephone: 323 442 2128, Fax: 323 442 2874. or to: Xiaoshun He, MD, PhD, Organ Transplant center, 1st affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, P.R. China; Tel: +86 20 87306082; Fax: +86 20 87306082; [email protected].. The authors declare no competing economic interests.AUTHOR CONTRIBUTIONS All authors had been involved in drafting the short article or revising it critically for crucial intellectual content, and all authors authorized the final version to become published. Dr. Zheng had complete access to all the information in the study and requires duty for the integrity with the data and the accuracy on the information analysis. Study conception and design. Zheng, Le, He, Huang. Acquisition of data. Chen, Su, Lin, Guo, Wang, Zhang. Analysis and interpretation of information. Chen, Lin, Guo, Huang, Liu, Brand, Ryffel.Chen et al.PageMethods–CIA has been induced with the immunization of sort II collagen (CII) and CFA in DBA/1J mice. GMSCs were injected i.v. into mice on day 14 right after immunization. In some experiments, injection of PC61 (anti-CD25 antibody) i.p. was made use of to delete Tregs in arthritic mice. Results–Infusion of GMSCs in DBA/1J mice with CIA drastically decreased the severity of arthritis and pathology scores, and down-regulated inflammatory cytokine (IFN-, IL-17A) production. Infusion of GMSCs resulted in an increase in CD4+CD39+Foxp3+ cells in arthritic mice. These increases had been noted early in spleen and LN and later in synovial fluid. The increased frequency of Foxp3+ Treg cells consisted of cells that had been primarily Helios damaging. Infusion of GMSCs partially interfered using the progress of CIA when Treg cells were depleted. Pre-treatment of GMSCs with CD39 or CD73 inhibitor significantly reversed the protective effect of GMSCs on CIA. Adenosine A3 receptor (A3R) Inhibitor supplier Conclusion–The role of GMSCs in controlling CIA pathology mostly depends upon CD39/ CD73 signals and partially upon the induction of CD4+CD39+Foxp3+ Treg cells. GMSCs present a promising strategy for the treatment of autoimmune illnesses. Rheumatoid arthritis (RA) is usually a symmetric polyarticular arthritis that mostly affects the little diarthrodial joints of body (1). Clinical drug development for therapy of RA has progressed gradually. At present, only about half of RA individuals respond to most.