title: Human Gingiva-Derived Mesenchymal Stem Cells Inhibit Xeno-Graft-versus-Host DiseaseviaCD39-CD73-Adenosine and IDO Signals.
abstract: Mesenchymal stem cells have the capacity to maintain immune homeostasis and prevent autoimmunity. We recently reported that human-derived gingival mesenchymal stem cells (GMSCs) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis in animals. However, it is unclear whether these cells can suppress human T cell-mediated diseases. Here, we used a xenogenic GVHD model in the NOD/SCID mouse, which is a useful preclinical construct for evaluating the therapeutic and translational potential of this approach for applications in human disease. We found that GMSCs potently suppressed the proliferation of PBMC and T cellsin vitro. Co-transfer of GMSC with human PBMC significantly suppressed human cell engraftment and markedly prolonged the mouse survival. Moreover, we demonstrated that GMSCs inhibited human PBMC-initiated xenogenic responsesviaCD39/CD73/adenosine and IDO signals. These findings suggest the potential for GMSCs to suppress human immune responses in immune system-mediated diseases, offering a potential clinical option to be used for modulating GVHD and autoimmune diseases.
authors.affiliation: Department of Clinical Immunology, Third Affiliated Hospital at Sun Yat-sen University , Guangzhou , China.
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.affiliation: Organ Transplant Center, First Affiliated Hospital at Sun Yat-sen University , Guangzhou , China.
authors.forename: Maogen
authors.initials: M
authors.lastname: Chen
authors.affiliation: Division of Rheumatology, Penn State Hershey College of Medicine , Hershey, PA , USA.
authors.forename: Weiqian
authors.initials: W
authors.lastname: Chen
authors.affiliation: Division of Rheumatology, Penn State Hershey College of Medicine , Hershey, PA , USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Clinical Immunology, Third Affiliated Hospital at Sun Yat-sen University , Guangzhou , China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Clinical Immunology, Third Affiliated Hospital at Sun Yat-sen University , Guangzhou , China.
authors.forename: Yaoqiu
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Clinical Immunology, Third Affiliated Hospital at Sun Yat-sen University , Guangzhou , China.
authors.forename: Junlong
authors.initials: J
authors.lastname: Dang
authors.affiliation: Department of Clinical Immunology, Third Affiliated Hospital at Sun Yat-sen University , Guangzhou , China.
authors.forename: Wenru
authors.initials: W
authors.lastname: Su
authors.affiliation: Division of Rheumatology, Penn State Hershey College of Medicine , Hershey, PA , USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Division of Periodontology, Diagnostic Sciences and Dental Hygiene, University of Southern California Ostrow School of Dentistry , Los Angeles, CA , USA.
authors.forename: Homayoun H
authors.initials: HH
authors.lastname: Zadeh
authors.affiliation: Organ Transplant Center, First Affiliated Hospital at Sun Yat-sen University , Guangzhou , China.
authors.forename: Xiaoshun
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Clinical Immunology, Third Affiliated Hospital at Sun Yat-sen University , Guangzhou , China.
authors.forename: Limin
authors.initials: L
authors.lastname: Rong
authors.affiliation: Division of Rheumatology, Penn State Hershey College of Medicine , Hershey, PA , USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Olsen
authors.affiliation: Department of Clinical Immunology, Third Affiliated Hospital at Sun Yat-sen University, Guangzhou, China; Division of Rheumatology, Penn State Hershey College of Medicine, Hershey, PA, USA.
authors.forename: Song Guo
authors.initials: SG
authors.lastname: Zheng
keywords: CD39; CD73; GVHD; adenosine; gingival mesenchymal stem cell; immune regulation; indoleamine 2,3-dioxygenase