title: Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells.
abstract: Mesenchymal stem cells (MSCs) from rodents and humans have been shown to suppress T cells by distinct primary pathways, with nitric oxide (NO)-dependent pathways dominating in rodents and indoleamine 2,3-deoxygenase (IDO)-dependent pathways dominating in humans. However, the immune suppressive pathways utilized by canine MSC have not been thoroughly studied, nor have bone marrow-derived MSC (BM-MSC) and adipose-derived MSC (Ad-MSC) been directly compared for their immune modulatory potency or pathway utilization. Therefore, canine BM-MSC and Ad-MSC were generated in vitro and their potency in suppressing T cell proliferation and cytokine production was compared, and differential gene expression. Mechanisms of T cells suppression were also investigated for both MSC types. We found that BM-MSC and Ad-MSC were roughly equivalent in terms of their ability to suppress T cell activation. However, the two MSC types used both shared and distinct biochemical pathways to suppress T cell activation. Ad-MSC utilized TGF-β signaling pathways and adenosine signaling to suppress T cell activation, whereas BM-MSC used cyclooxygenase, TGF-β and adenosine signaling pathways to suppress T cell activation. These results indicate that canine MSC are distinct from human and rodent MSC terms of their immune suppressive pathways, relying primarily on cyclooxygenase and TGF-β pathways for T cell suppression, rather than on NO or IDO-mediated pathways.
authors.affiliation: 1 Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Ft. Collins, Colorado.|2 Center for Immune and Regenerative Medicine, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Ft. Collins, Colorado.
authors.forename: Lyndah
authors.initials: L
authors.lastname: Chow
authors.affiliation: 1 Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Ft. Collins, Colorado.|2 Center for Immune and Regenerative Medicine, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Ft. Collins, Colorado.
authors.forename: Valerie
authors.initials: V
authors.lastname: Johnson
authors.affiliation: 1 Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Ft. Collins, Colorado.|2 Center for Immune and Regenerative Medicine, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Ft. Collins, Colorado.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Coy
authors.affiliation: 1 Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Ft. Collins, Colorado.|2 Center for Immune and Regenerative Medicine, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Ft. Collins, Colorado.
authors.forename: Dan
authors.initials: D
authors.lastname: Regan
authors.affiliation: 1 Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Ft. Collins, Colorado.|2 Center for Immune and Regenerative Medicine, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Ft. Collins, Colorado.
authors.forename: Steven
authors.initials: S
authors.lastname: Dow
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004285:Dogs; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
chemical_list: D016207:Cytokines; D007371:Interferon-gamma
keywords: T cell; cytokines; dog; stem cell