title: Th17 Pathway As a Target for Multipotent Stromal Cell Therapy in Dogs: Implications for Translational Research.
abstract: Detrimental Th17 driven inflammatory and autoimmune disease such as Crohn's disease, graft versus host disease and multiple sclerosis remain a significant cause of morbidity and mortality worldwide. Multipotent stromal/stem cell (MSC) inhibit Th17 polarization and activation in vitro and in rodent models. As such, MSC based therapeutic approaches are being investigated as novel therapeutic approaches to treat Th17 driven diseases in humans. The significance of naturally occurring diseases in dogs is increasingly recognized as a realistic platform to conduct pre-clinical testing of novel therapeutics. Full characterization of Th17 cells in dogs has not been completed. We have developed and validated a flow-cytometric method to detect Th17 cells in canine blood. We further demonstrate that Th17 and other IL17 producing cells are present in tissues of dogs with naturally occurring chronic inflammatory diseases. Finally, we have determined the kinetics of a canine specific Th17 polarization in vitro and demonstrate that canine MSC inhibit Th17 polarization in vitro, in a PGE2 independent mechanism. Our findings provide fundamental research tools and suggest that naturally occurring diseases in dogs, such as inflammatory bowel disease, may be harnessed to translate novel MSC based therapeutic strategies that target the Th17 pathway.
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California, 95616, United States of America.
authors.forename: A
authors.initials: A
authors.lastname: Kol
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California, 95616, United States of America.
authors.forename: N J
authors.initials: NJ
authors.lastname: Walker
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California, 95616, United States of America.
authors.forename: M
authors.initials: M
authors.lastname: Nordstrom
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California, 95616, United States of America.
authors.forename: D L
authors.initials: DL
authors.lastname: Borjesson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003872:Dermatitis / Q000276:immunology / Q000473:pathology / Q000628:therapy / Q000662:veterinary; D004283:Dog Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004285:Dogs; D005786:Gene Expression Regulation; D005891:Gingivitis / Q000276:immunology / Q000473:pathology / Q000628:therapy / Q000662:veterinary; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy / Q000662:veterinary; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D008590:Meningoencephalitis / Q000276:immunology / Q000473:pathology / Q000628:therapy / Q000662:veterinary; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D054399:Receptors, CCR6 / Q000235:genetics / Q000276:immunology; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D057170:Translational Research, Biomedical / Q000379:methods
chemical_list: D020381:Interleukin-17; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D054399:Receptors, CCR6; D018123:Receptors, Interleukin