title: The Synergistic Local Immunosuppressive Effects of Neural Stem Cells Expressing Indoleamine 2,3-Dioxygenase (IDO) in an Experimental Autoimmune Encephalomyelitis (EAE) Animal Model.
abstract: Neurodegenerative diseases provoke robust immunological reactions in the central nervous system (CNS), which further deteriorate the neural tissue damage. We hypothesized that the expression levels of indoleamine 2,3-dioxygenase (IDO), an enzyme that has potent immune suppressive activities, in neural stem cells (NSCs) would have synergistic therapeutic effects against neurodegenerative diseases, since NSCs themselves have low IDO expression. In this study, the synergistic immune suppressive effects of rat fetal NSCs expressing IDO (rfNSCs-IDO) were validated by mixed leukocyte reaction (MLR) in vitro and an experimental autoimmune encephalomyelitis (EAE) animal model in vivo. rfNSCs-IDO showed significantly more suppressive effects on T cell proliferation in the MLR compared to control rfNSCs (rfNSCs-Cont). Importantly, IDO inhibition using 1-methyl-DL-tryptophan (1-MT), an IDO inhibitor, reversed the synergistic effects, confirming IDO-specific effects in rfNSCs-IDO. In the EAE animal model, systemic rfNSCs-IDO injections resulted in significant local immune suppression in the cervical lymph nodes and CNS, evidenced by a reduction in the number of activated T lymphocytes and an increase in regulatory T cell numbers, which induced significantly fewer clinical symptoms and faster recovery. In contrast, rfNSCs-Cont failed to reduce symptoms in the EAE animal models, although they showed local immune suppression, which was significantly less than that in rfNSCs-IDO. Taken together, IDO expression in NSCs synergistically potentiates the immune suppression activities of NSCs and could be applicable for the development of therapeutic modalities against various neurodegenerative diseases.
authors.affiliation: Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Young Eun
authors.initials: YE
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jaeyeol
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kee-Hang
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sung Su
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Song
authors.affiliation: Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Heejang
authors.initials: H
authors.lastname: Pyeon
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Nam
authors.affiliation: Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Kyeongjin
authors.initials: K
authors.lastname: Kang
authors.affiliation: Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.|Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.|Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology*; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology*; D058953:Neural Stem Cells / Q000276:immunology* / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase