title: Suppression of Th1-mediated autoimmunity by embryonic stem cell-derived dendritic cells.
abstract: We herein demonstrate the immune-regulatory effect of embryonic stem cell-derived dendritic cells (ES-DCs) using two models of autoimmune disease, namely non-obese diabetic (NOD) mice and experimental autoimmune encephalomyelitis (EAE). Treatment of pre-diabetic NOD mice with ES-DCs exerted almost complete suppression of diabetes development during the observation period for more than 40 weeks. The prevention of diabetes by ES-DCs was accompanied with significant reduction of insulitis and decreased number of Th1 and Th17 cells in the spleen. Development of EAE was also inhibited by the treatment with ES-DCs, and the therapeutic effect was obtained even if ES-DCs were administrated after the onset of clinical symptoms. Treatment of EAE-induced mice with ES-DCs reduced the infiltration of inflammatory cells into the spinal cord and suppressed the T cell response to the myelin antigen. Importantly, the ES-DC treatment did not affect T cell response to an exogenous antigen. As the mechanisms underlying the reduction of the number of infiltrating Th1 cells, we observed the inhibition of differentiation and proliferation of Th1 cells by ES-DCs. Furthermore, the expression of VLA-4α on Th1 cells was significantly inhibited by ES-DCs. Considering the recent advances in human induced pluripotent stem cell-related technologies, these results suggest a clinical application for pluripotent stem cell-derived dendritic cells as a therapy for T cell-mediated autoimmune diseases.
authors.affiliation: Department of Immunogenetics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; Japan Science and Technology Agency, CREST, Kawaguchi, Japan.
authors.forename: Tokunori
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Hematology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hirata
authors.affiliation: Department of Immunogenetics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; Japan Science and Technology Agency, CREST, Kawaguchi, Japan; Department of Neurology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Takamatsu
authors.affiliation: Department of Immunogenetics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; Japan Science and Technology Agency, CREST, Kawaguchi, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Haruta
authors.affiliation: Department of Immunogenetics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Tsukamoto
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
authors.affiliation: Jonan Hospital, Kumamoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchino
authors.affiliation: Department of Neurology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.affiliation: Department of Medical Science and Technology, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Seiho
authors.initials: S
authors.lastname: Nagafuchi
authors.affiliation: Department of Immunogenetics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Immunogenetics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; Japan Science and Technology Agency, CREST, Kawaguchi, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D053595:Embryonic Stem Cells / Q000166:cytology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018417:Th1 Cells / Q000276:immunology*