title: Intraperitoneal injection of IDO-expressing dermal fibroblasts improves the allograft survival.
abstract: Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme with tolerogenic effects on different immune cells. Our group has previously shown that co-transplantation of IDO-expressing fibroblasts with donor tissues can delay immune rejection by inducing local immunosuppression. In this study, we have employed a systemic approach to improve allograft survival without using any immunosuppressive medication. To achieve this, 10 million lentiviral transduced IDO-expressing donor derived fibroblasts were injected into the peritoneal cavity of allograft recipients. We showed that IDO-fibroblast therapy increases the survival of both islets and skin allografts and decreases the infiltration of immune cells in subcutaneous transplanted skins. Indirect pathway of allo-reactive T cell activation was suppressed more than the direct pathway. Injected IDO-fibroblasts were found in peritoneal cavity and mesenteric lymph nodes of the recipient mice. In conclusion, IDO-expressing fibroblast therapy proved to be a novel approach in improving the allogeneic graft survival.
authors.affiliation: Department of Surgery/Division of Plastic Surgery, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khosravi-Maharlooei
authors.affiliation: Department of Surgery/Division of Plastic Surgery, University of British Columbia, Vancouver, BC, Canada.
authors.forename: MohammadReza
authors.initials: M
authors.lastname: Pakyari
authors.affiliation: Department of Surgery/Division of Plastic Surgery, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Reza B
authors.initials: RB
authors.lastname: Jalili
authors.affiliation: Department of Surgery/Division of Plastic Surgery, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Ruhangiz T
authors.initials: RT
authors.lastname: Kilani
authors.affiliation: Department of Surgery/Division of Plastic Surgery, University of British Columbia, Vancouver, BC, Canada. Electronic address: aghahary@mail.ubc.ca.
authors.forename: Aziz
authors.initials: A
authors.lastname: Ghahary
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D005260:Female; D005347:Fibroblasts / Q000637:transplantation*; D006085:Graft Survival; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007274:Injections, Intraperitoneal; D016381:Islets of Langerhans Transplantation; D008297:Male; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012867:Skin / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase
keywords: Allograft survival; Fibroblast; Indoleamine 2,3-dioxygenase